<?xml version="1.0" encoding="UTF-8"?><!DOCTYPE article  PUBLIC "-//NLM//DTD Journal Publishing DTD v3.0 20080202//EN" "http://dtd.nlm.nih.gov/publishing/3.0/journalpublishing3.dtd"><article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" dtd-version="3.0" xml:lang="en" article-type="research article"><front><journal-meta><journal-id journal-id-type="publisher-id">OALibJ</journal-id><journal-title-group><journal-title>Open Access Library Journal</journal-title></journal-title-group><issn pub-type="epub">2333-9705</issn><publisher><publisher-name>Scientific Research Publishing</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.4236/oalib.1110520</article-id><article-id pub-id-type="publisher-id">OALibJ-127077</article-id><article-categories><subj-group subj-group-type="heading"><subject>Articles</subject></subj-group><subj-group subj-group-type="Discipline-v2"><subject>Biomedical&amp;Life Sciences</subject><subject> Business&amp;Economics</subject><subject> Chemistry&amp;Materials Science</subject><subject> Computer Science&amp;Communications</subject><subject> Earth&amp;Environmental Sciences</subject><subject> Engineering</subject><subject> Medicine&amp;Healthcare</subject><subject> Physics&amp;Mathematics</subject><subject> Social Sciences&amp;Humanities</subject></subj-group></article-categories><title-group><article-title>
 
 
  Biotechnological Drug Development—The Role of Proteins, Genes, &lt;i&gt;In-Silico&lt;/i&gt;, and Stem Cells in Designing Models for Enhanced Drug Discovery
 
</article-title></title-group><contrib-group><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Taofik</surname><given-names>Ahmed Suleiman</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Ann</surname><given-names>Christopher Francis</given-names></name><xref ref-type="aff" rid="aff2"><sup>2</sup></xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Abdulwasiu</surname><given-names>Ibrahim</given-names></name><xref ref-type="aff" rid="aff3"><sup>3</sup></xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Adedoyin</surname><given-names>Owolade Jonn-Joy</given-names></name><xref ref-type="aff" rid="aff4"><sup>4</sup></xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Ebenezer</surname><given-names>Adebiyi</given-names></name><xref ref-type="aff" rid="aff5"><sup>5</sup></xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Daniel</surname><given-names>Tweneboah Anyimadu</given-names></name><xref ref-type="aff" rid="aff6"><sup>6</sup></xref></contrib></contrib-group><aff id="aff3"><addr-line>Department of Biochemistry and Molecular Biology, Usman Danfodiyo University, Sokoto, Nigeria</addr-line></aff><aff id="aff2"><addr-line>Department of Biotechnology, University of Texas at Tyler Health Science Center, Tyler, USA</addr-line></aff><aff id="aff4"><addr-line>Department of Pharmacy, Obafemi Awolowo University, Ile-Ife, Nigeria</addr-line></aff><aff id="aff5"><addr-line>Department of Chemistry, Federal University of Technology Akure, Akure, Nigeria</addr-line></aff><aff id="aff1"><addr-line>Department of Medical Imaging and Computing, University of Girona, Girona, Spain</addr-line></aff><aff id="aff6"><addr-line>Graduate School of Science and Technology, Medical Imaging and Applications (MAIA), University of Burgundy, Le Creusot, France</addr-line></aff><pub-date pub-type="epub"><day>31</day><month>07</month><year>2023</year></pub-date><volume>10</volume><issue>08</issue><fpage>1</fpage><lpage>20</lpage><history><date date-type="received"><day>18,</day>	<month>July</month>	<year>2023</year></date><date date-type="rev-recd"><day>15,</day>	<month>August</month>	<year>2023</year>	</date><date date-type="accepted"><day>18,</day>	<month>August</month>	<year>2023</year></date></history><permissions><copyright-statement>&#169; Copyright  2014 by authors and Scientific Research Publishing Inc. </copyright-statement><copyright-year>2014</copyright-year><license><license-p>This work is licensed under the Creative Commons Attribution International License (CC BY). http://creativecommons.org/licenses/by/4.0/</license-p></license></permissions><abstract><p>
 
 
  The application of biotechnology in drug discovery has been discovered to be a promising and resourceful approach for the discovery of novel therapeutic candidates that comes with less time and cost than the traditional ways of drug discovery. This has additionally endowed researchers with the necessary understanding of diseases, which offers exceptional methods for treating patients. Additionally, diagnosis and treatment are becoming increasingly intertwined with the help of biotechnology. Today, researchers in biotechnology deal with the root of diseases and find solutions through therapeutic agents, hence, improving quality of life. The discovery of drugs in recent days is practically challenging without good modeling in biotechnology, this wonderful technique is now being adopted in the discovery of new and effective classes of drugs which include but are not limited to gene therapy, cancer vaccines, proteins, and even enzymes. In this current review, we review the efforts so far in the usage of this approach in drug discovery. The review targets the biotechnological application and design implementation in drug discovery. It explains the use of proteins, genes, 
  in-silico, and stem cells in designing models for enhanced drug discovery, the chemical similarity network for drug discovery, and future recommendations on the integration of AI in biotechnology.
 
</p></abstract><kwd-group><kwd>Drug Discovery</kwd><kwd> Biotechnology</kwd><kwd> Diseases</kwd><kwd> Genes</kwd><kwd> Protein</kwd><kwd> &lt;i&gt;In-Silico&lt;/i&gt;</kwd><kwd> Stem Cells</kwd><kwd> mRNA</kwd><kwd> DNA</kwd></kwd-group></article-meta></front><body><sec id="s1"><title>1. Introduction</title><p>The word “biotechnology,” which appears to have originated in the 1970s, is now widely used by researchers across different fields to signify different things based on their applications [<xref ref-type="bibr" rid="scirp.127077-ref1">1</xref>] . The relevant general definition of biotechnology is the use of organisms and their biological systems for practical and manufacturing processes [<xref ref-type="bibr" rid="scirp.127077-ref2">2</xref>] . Biotechnology can alternatively be defined as the fusion of biology and technology, thus for all intents and purposes implying the enclosure of all biological and related technologies in product alteration [<xref ref-type="bibr" rid="scirp.127077-ref3">3</xref>] . This further implies that biotechnology is a form of genetic engineering, specifically with cutting-edge molecular processes such as recombinant DNA, which use biological catalysts (enzymes) known as restriction endonuclease to cut and splice (or recombine) DNA fragments into large numbers of fragments [<xref ref-type="bibr" rid="scirp.127077-ref4">4</xref>] . Biotechnology is now recognized by biomedical science researchers as a front-line approach to solving most of the world’s health challenges, including one-health, infectious, and non-infectious diseases [<xref ref-type="bibr" rid="scirp.127077-ref5">5</xref>] , and scientists have used biotechnology knowledge for disease management over the last few decades [<xref ref-type="bibr" rid="scirp.127077-ref2">2</xref>] . The therapeutic yields of biotechnologies, known as biologics or biopharmaceuticals, are now at the forefront of delivering insights and advancements for the treatment of a wide range of human diseases, including microbial infections, diabetes, and malignancies. This has further demonstrated the usefulness of biotechnology in drug discovery over traditional methods [<xref ref-type="bibr" rid="scirp.127077-ref2">2</xref>] .</p><p>Traditional drug discovery has been reported to be a costly and complex process requiring several billions of dollars, with thousands of chemicals failing before clinical trials representing 99% of the starting chemical compounds; of these chemical compounds assessed as part of drug discovery and preclinical testing, only a few made it to human clinical trials and were eventually accepted for commercial use by the Food and Drug Administration (FDA) [<xref ref-type="bibr" rid="scirp.127077-ref4">4</xref>] . Following these setbacks gave birth to a novel therapeutic development strategy based on genomic and proteomic know-how that has technologically progressed over the years in minimizing these challenges [<xref ref-type="bibr" rid="scirp.127077-ref5">5</xref>] . The genome that is, the full makeup of an organism’s genetic information that includes both coding and non-coding nucleic acid sequences provides a framework for characterizing the proteome, which is a list of only the encoding nucleic acid regions that result in the biosynthesis of protein products [<xref ref-type="bibr" rid="scirp.127077-ref1">1</xref>] . The study of genes and proteins aids in the discovery of new genes and proteins, as well as the evaluation of their levels in diseased cells, normal cells, and cells treated with a variety of chemicals with varying efficacy and toxicity [<xref ref-type="bibr" rid="scirp.127077-ref1">1</xref>] . As a result, they come in handy when it comes to identifying new therapeutic targets [<xref ref-type="bibr" rid="scirp.127077-ref5">5</xref>] .</p><p>This review article discusses some of the techniques used in biotechnological drug discovery and development.</p></sec><sec id="s2"><title>2. Overview and Design Implementation of Biotechnological Drug Discovery of Cancer Management</title><p>The use of a biotechnological approach to drug discovery has become prominent in research and development; biopharmaceuticals, which are products of the use of biotechnology in discovering new drug targets have generated revenues for several pharmaceutical companies, which is an indication of its importance in drug discovery [<xref ref-type="bibr" rid="scirp.127077-ref6">6</xref>] [<xref ref-type="bibr" rid="scirp.127077-ref7">7</xref>] . Over the years, biotechnological approaches such as whole-genome profiling and sequencing, proteomics, and microarray techniques have birthed positive innovations in discovering novel drug targets to cure certain diseases, most especially cancer [<xref ref-type="bibr" rid="scirp.127077-ref6">6</xref>] . The role of genomics and proteomics in achieving this cannot be over-emphasized.</p><sec id="s2_1"><title>2.1. Role of Genomics in Biotechnological Drug Discovery</title><p>Numerous diseases, such as diabetes, autoimmune disorders, neurological disorder, and cancer are caused because of dysregulation of a complex interplay of genes [<xref ref-type="bibr" rid="scirp.127077-ref8">8</xref>] . One of the most advanced and innovative techniques used by biotechnological researchers is genomics, which incorporates genomic sequence and human genome analysis. The knowledge of genomics has empowered researchers to adopt a more represented strategy in developing safe and effective drugs. Genome sequencing can predict the risk of developing diseases, the origin, traits, and response to drugs. With profound knowledge of genomic data, organizations are currently ready to develop drugs that affect pathogens or cancer cells, without causing any harm to healthy body cells [<xref ref-type="bibr" rid="scirp.127077-ref9">9</xref>] . In addition, vast knowledge in genomics can proffer further ideas into the mechanism of drug action, which contributes to discovering novel therapeutic agents [<xref ref-type="bibr" rid="scirp.127077-ref10">10</xref>] . Furthermore, dissimilarities in the genomic makeup in humans present a surplus opening for effective drug discovery [<xref ref-type="bibr" rid="scirp.127077-ref11">11</xref>] , identification of target molecule, and evolving drug leads to the apt likelihood for preclinical and clinical studies [<xref ref-type="bibr" rid="scirp.127077-ref12">12</xref>] . The use of gene studies in the preclinical setting necessitates one to screen numerous compounds with negligible discrepancy. At the point when the target gene is isolated, the chemical that works best largely in contradiction of all its subtypes is picked for further studies [<xref ref-type="bibr" rid="scirp.127077-ref13">13</xref>] .</p><p>Other sources which integrate genomic data at the notch of chromosomal DNA, disease-associated genes, mRNA transcript sum up of tissues, genetic difference data in humans, and animal and developmental modes applicable to disease all embrace genomic methods [<xref ref-type="bibr" rid="scirp.127077-ref14">14</xref>] . For illustration, if the disease target implicates human endothelium, genomic data on the target organ context can be quarried with bioinformatics for the discovery process. The adoption of transcriptional arrays or DNA sequencing of a complementary DNA library of human endothelial cells provides a standpoint on gene transcription in the human endothelium. Likewise, proteomics can give an understanding of the useful protein in specific cells [<xref ref-type="bibr" rid="scirp.127077-ref14">14</xref>] .</p></sec><sec id="s2_2"><title>2.2. Proteomics Approach in Biotechnological Drug Discovery</title><p>Quite a lot of studies have proven that genomics aids majorly in the identification of drug-target processes since it is considered a high throughput screening of expressed genes. Also, the work of Zhang et al., highlighted several works of literature to show that the analysis of the genome does not account for the post-translational process, which takes account of protein amendment and protein metabolism [<xref ref-type="bibr" rid="scirp.127077-ref15">15</xref>] . Genomics is positioned on genetic data, while proteomics considers genetic data of DNA or mRNA, as well as protein post-translational modification. Thus, the practices involved in the discovery of drugs moved from genomics to proteomics. Yet, the discovery of molecular targets for specific diseases requires the understanding and utilization of both genomic and proteomic methods at the biochemical and physiological levels [<xref ref-type="bibr" rid="scirp.127077-ref15">15</xref>] .</p><p>Proteomics has attained a lot of consideration as a drug development platform [<xref ref-type="bibr" rid="scirp.127077-ref13">13</xref>] , the skills adopted in proteomics can give a wide-ranging evaluation of countless activities in clinical research of numerous diseases [<xref ref-type="bibr" rid="scirp.127077-ref16">16</xref>] . As most drugs bind to proteins or nucleic acid (enzymes, ion channels, or receptors) [<xref ref-type="bibr" rid="scirp.127077-ref17">17</xref>] , the proteomics model embroils trailing an unstable protein that is prompting a harmful effect, and subsequently, the application of a drug molecule to revise its effect [<xref ref-type="bibr" rid="scirp.127077-ref18">18</xref>] . The proteomics approach involves; 1) Target identification and validation, 2) Biomarker identification (Efficacy and safety) [<xref ref-type="bibr" rid="scirp.127077-ref19">19</xref>] .</p><sec id="s2_2_1"><title>2.2.1. Target Identification and Validation</title><p>Target identification and validation make sure the protein (biological target) is druggable; the activity of the protein can be restrained and change the state of the disease (therapeutic effect), these proteins can then be employed to classify patients for clinical trials [<xref ref-type="bibr" rid="scirp.127077-ref20">20</xref>] .</p></sec><sec id="s2_2_2"><title>2.2.2. Biomarkers Identification</title><p>Biomarkers are customarily hired in each phase of drug discovery; the use of biomarkers has the potential to speed up the drug discovery process and approval procedures [<xref ref-type="bibr" rid="scirp.127077-ref21">21</xref>] . The ability of biomarkers is exploited during preclinical studies, to distinguish disease models, and investigate the consequence and mechanism of action of the lead drug candidates in vivo models [<xref ref-type="bibr" rid="scirp.127077-ref20">20</xref>] . In addition, the toxicity of biomarkers informs the presence or degree of toxicity, increasing confidence in safety, and the ability to forecast, detect and track drug-induced toxicity progression. The sum of the efficacy and impact of biomarkers toxicity in preclinical and clinical drug discovery will be strong-minded by their ability to detect early toxicity, monitor onset, and reversibility, and succeed in adverse effects detected in the clinical studies [<xref ref-type="bibr" rid="scirp.127077-ref22">22</xref>] . <xref ref-type="table" rid="table1">Table 1</xref> highlights the major differences between genomics and proteomics approaches to drug discovery.</p></sec></sec><sec id="s2_3"><title>2.3. Design Implementation of Biotechnological Drug Discovery</title><p>The use of biotechnology in drug discovery is a broad area and yet growing and famous field [<xref ref-type="bibr" rid="scirp.127077-ref27">27</xref>] . Effective quality and design are implemented in biotechnological drug discovery to allow persistent drug delivery and increase drug performance [<xref ref-type="bibr" rid="scirp.127077-ref28">28</xref>] . In support, biotechnological production is irreversible, very luxurious, and encompasses a lot of critical parameters throughout the process. Quality control tests applied to the intermediate and final product become inefficacious; therefore, sustaining predefined quality is vibrant [<xref ref-type="bibr" rid="scirp.127077-ref27">27</xref>] . The quality and design implementation in biotechnological drug discovery follows four key stages: 1) define a target; 2) design the product; 3) identify potential risk, and 4) develop a control strategy [<xref ref-type="bibr" rid="scirp.127077-ref27">27</xref>] [<xref ref-type="bibr" rid="scirp.127077-ref29">29</xref>] .</p><table-wrap id="table1" ><label><xref ref-type="table" rid="table1">Table 1</xref></label><caption><title> Major differences between genomics and proteomics approaches to drug discovery</title></caption><table><tbody><thead><tr><th align="center" valign="middle" >Parameters</th><th align="center" valign="middle" >Genomics</th><th align="center" valign="middle" >Proteomics</th></tr></thead><tr><td align="center" valign="middle" >Definition</td><td align="center" valign="middle" >The study of an organism’s entire genome, including genes, regulatory regions, and non-coding regions</td><td align="center" valign="middle" >The study of an organism’s entire set of proteins, including their structure, function, and interactions</td></tr><tr><td align="center" valign="middle" >Focus</td><td align="center" valign="middle" >Identification of genes and their function</td><td align="center" valign="middle" >Identification of proteins and their function</td></tr><tr><td align="center" valign="middle" >Key Techniques</td><td align="center" valign="middle" >DNA sequencing, genome-wide association studies, transcriptomics</td><td align="center" valign="middle" >Mass spectrometry, protein microarrays, protein-protein interaction analysis</td></tr><tr><td align="center" valign="middle" >Output</td><td align="center" valign="middle" >Identification of potential drug targets based on genetic variants and gene expression patterns</td><td align="center" valign="middle" >Identification of potential drug targets based on protein expression patterns and protein-protein interactions</td></tr><tr><td align="center" valign="middle" >Advantages</td><td align="center" valign="middle" >Provides a comprehensive view of an organism’s genetic makeup and potential drug targets</td><td align="center" valign="middle" >Identifies proteins that are actively involved in disease processes and may be more relevant drug targets than genes</td></tr><tr><td align="center" valign="middle" >Limitations</td><td align="center" valign="middle" >Identifying relevant genes and their functions can be challenging, as many genes have multiple functions and interact with each other</td><td align="center" valign="middle" >Protein identification and analysis can be complex and expensive, and it may be difficult to identify relevant proteins among the vast number of proteins in a cell or tissue</td></tr><tr><td align="center" valign="middle" >References</td><td align="center" valign="middle" >[<xref ref-type="bibr" rid="scirp.127077-ref23">23</xref>] [<xref ref-type="bibr" rid="scirp.127077-ref24">24</xref>]</td><td align="center" valign="middle" >[<xref ref-type="bibr" rid="scirp.127077-ref25">25</xref>] [<xref ref-type="bibr" rid="scirp.127077-ref26">26</xref>]</td></tr></tbody></table></table-wrap><sec id="s2_3_1"><title>2.3.1. Define a Target Product Profile/Goals</title><p>To design quality into a product, the product design and performance stipulations must be well understood at the beginning of the design phase [<xref ref-type="bibr" rid="scirp.127077-ref27">27</xref>] . The profile of a target product is an exceptional and vigorous synopsis of the quality features of a drug product that supremely will be realized to facilitate the desired quality, safety, and efficacy of a drug product is succeeded [<xref ref-type="bibr" rid="scirp.127077-ref29">29</xref>] [<xref ref-type="bibr" rid="scirp.127077-ref30">30</xref>] . Significant target product profile takes account of dosage form and route of administration, dosage form strength(s), therapeutic moiety release, and pharmacokinetic characteristics suitable to the drug product dosage form being developed and drug product quality appropriate for the desired marketed product [<xref ref-type="bibr" rid="scirp.127077-ref31">31</xref>] .</p></sec><sec id="s2_3_2"><title>2.3.2. Design Product</title><p>For the innovation of a novel pharmaceutical product, the following system is followed by rub in the enactment of quality by design practically [<xref ref-type="bibr" rid="scirp.127077-ref31">31</xref>] [<xref ref-type="bibr" rid="scirp.127077-ref32">32</xref>] [<xref ref-type="bibr" rid="scirp.127077-ref33">33</xref>] [<xref ref-type="bibr" rid="scirp.127077-ref34">34</xref>] : 1) The product’s preferred performance is defined by ascertaining the quality of the target product profile; 2) Serious quality traits identification; 3) Recognition of credible critical process factors and critical material elements; 4) Connotation of design of experiment with critical substantial characteristics and serious process factors to critical quality elements to obtain adequate data and how these variables quality target product profile. Thus, describe the design space, prominent to a product with a desired quality target product profile. The design product must satisfy predefined objectives.</p></sec><sec id="s2_3_3"><title>2.3.3. Risk Assessment</title><p>An exact problem sketch or risk question is the inauguration of a quality risk assessment. If the risk in question is well structured, a proper risk-controlling tool and the types of data necessary to attend to the risk question will be more enthusiastically dogged [<xref ref-type="bibr" rid="scirp.127077-ref27">27</xref>] . A proficient quality risk evaluation should be used in any biotechnological drug practice [<xref ref-type="bibr" rid="scirp.127077-ref28">28</xref>] . Contained by the drug discovery phase, the risk management approach ought to concentrate on hazard awareness, avoidance, and reduction. Input into the scheme and choice of compounds will be mandatory to reduce their potential to form reactive metabolites and exhibit proof of objectionable safety parameters [<xref ref-type="bibr" rid="scirp.127077-ref35">35</xref>] . This will consist of the use of machinery that can detect shortages of compounds and can be embraced repeatedly while having the aptitudes necessary in the design and analysis phase [<xref ref-type="bibr" rid="scirp.127077-ref35">35</xref>] .</p></sec><sec id="s2_3_4"><title>2.3.4. Control Strategy</title><p>The control approach is a series of strategic controls, ascending from invention and process thoughtful that licenses procedure performance and product quality. The controls can entail parameters and elements and it is alarmed with the medicinal material and drug product materials and components, facility and kit operating settings, and the obligatory approaches and density of reflection and audit, comparability tests and strength testing [<xref ref-type="bibr" rid="scirp.127077-ref27">27</xref>] [<xref ref-type="bibr" rid="scirp.127077-ref36">36</xref>] . The likelihood of a harmful impact on product efficacy can be reduced by an all-inclusive method to the control strategy. A control strategy for a product object to offer that significant controls are in domicile to hunt the risks associated with the product at an acceptable limit. Hence, the understanding of risk management and control strategy are momentously connected and the use of risk evaluation in creating the control strategy is exclusive to the quality design approach [<xref ref-type="bibr" rid="scirp.127077-ref27">27</xref>] . A well-established control strategy will diminish risk but does not change the criticality of qualities. The control strategy plays a fundamental role in guaranteeing that the serious process parameters are met, and therefore the quality target product profiles are apprehended [<xref ref-type="bibr" rid="scirp.127077-ref27">27</xref>] . <xref ref-type="fig" rid="fig1">Figure 1</xref> shows the steps involved in the design implementation of biotechnological drug discovery.</p></sec></sec></sec><sec id="s3"><title>3. The Role of Proteins, Genes, Stem Cells, and In-Silico in Drug Discovery</title><p>Isolating protein targets of biologically active compounds is a resourceful way to discover unidentified protein functions, and molecular mechanisms of drug action [<xref ref-type="bibr" rid="scirp.127077-ref37">37</xref>] . Within the worldwide pharmaceutical industry, protein-based drugs have been reported to reveal the firmest growth in recent years and presently have matchless credit for their potential as a practicable treatment choice for numerous diseases [<xref ref-type="bibr" rid="scirp.127077-ref1">1</xref>] . According to [<xref ref-type="bibr" rid="scirp.127077-ref38">38</xref>] , over 100 original proteins and an associated number of boosted proteins are approved for therapeutic clinical use in Europe and the USA, with 2010 sales of US$108 billion [<xref ref-type="bibr" rid="scirp.127077-ref38">38</xref>] [<xref ref-type="bibr" rid="scirp.127077-ref39">39</xref>] . In this group, monoclonal antibodies represent almost half (48%) of the sales. Protein therapeutics are used in the management of many major diseases including cancers, immune disorders, and infections [<xref ref-type="bibr" rid="scirp.127077-ref39">39</xref>] .</p><sec id="s3_1"><title>3.1. Protein Kinases as a Target for Drug Discovery</title><p>Protein kinases are at present one of the most detected classes of drug targets as established by the multiple kinase inhibitors that have arrived in clinical trials in recent years [<xref ref-type="bibr" rid="scirp.127077-ref37">37</xref>] [<xref ref-type="bibr" rid="scirp.127077-ref40">40</xref>] . Imatinib, a tyrosine kinase inhibitor, is a drug that is now approved by the food and drug administration (FDA) for the treatment of specific types of cancer. As there are over 500 known human protein kinases and most of them engage in adenosine triphosphate binding pocket which is extremely sealed, selectivity is a crucial issue [<xref ref-type="bibr" rid="scirp.127077-ref37">37</xref>] . The main use of protein for the advances of drug compounds is to identify the structure of a protein in a complex with a tool compound such as a lead inhibitor to give a new chemical postulate to enrich inhibitor affinity by signifying new chemical reforms [<xref ref-type="bibr" rid="scirp.127077-ref41">41</xref>] .</p></sec><sec id="s3_2"><title>3.2. Genome Sequences as a Foundation for Modern Drug Discovery</title><p>The importance of complete genome sequences for modern approaches to drug discovery can never be underestimated. Researchers now understand the full match of proteins encoded by the human genome, and most human proteins can be allocated into structurally and mechanistically allied folks based on sequence homology [<xref ref-type="bibr" rid="scirp.127077-ref42">42</xref>] . The study of gene purpose from high throughput studies of protein-protein collaborations can be divided into networks and pathways using bioinformatics data combination tools [<xref ref-type="bibr" rid="scirp.127077-ref43">43</xref>] . The sequence of the genome has given a comprehensive parts list elucidating all the proteins available in the human body, and high throughput screening techniques give podia for exposing these proteins to millions of small molecules [<xref ref-type="bibr" rid="scirp.127077-ref41">41</xref>] . Therefore, the role of protein and genome sequences cannot be overemphasized in today’s drug discovery.</p></sec><sec id="s3_3"><title>3.3. Stem Cells as Vitriol Models for Drug Discovery</title><p>The use of in vitro models in drug development has been a foremost enhancement, not only in the innovation of essential chemical compounds, but also in providing relevant information on their pharmacodynamics i.e. “absorption, distribution, metabolism, and excretion” (ADME) features [<xref ref-type="bibr" rid="scirp.127077-ref44">44</xref>] . The advance of several in vitro pharmacodynamics models has prepared a resilient influence on the pathway in the route of transforming and accelerating drug discovery and development. For example, engineered tumour eternalized cells obtained from humans or animals have remained the finest acknowledged in vitro approach used by the biotechnology and pharmaceutical industries [<xref ref-type="bibr" rid="scirp.127077-ref45">45</xref>] [<xref ref-type="bibr" rid="scirp.127077-ref46">46</xref>] . Though these cell lines own the aids of aptness and scalability of the selection process, they elucidate extraordinary patchiness in their advance, strange genotype, and biological reaction to pharmaceutical formulations. However, the irregularities associated with these eternalized cells edged the rate and figure of prime molecules for drug development. Another example is the practice of dedicated basic culture approaches such as hepatocytes, human umbilical endothelial cells, and keratinocytes delivered fractional practice owing to their synchronized expandability [<xref ref-type="bibr" rid="scirp.127077-ref47">47</xref>] . In this case, the obligation for an enriched and constant physiological reaction, typical genotype, and development configuration has redirected drug innovation determinations near the understanding of stem cells. Furthermore, the prospect of detaching stem cells from a huge continuum of tissues [<xref ref-type="bibr" rid="scirp.127077-ref48">48</xref>] and evolving them in vitro, as well as their competence to ghettoize into several proficient cell types, has delivered an instrumental means for drug/target sighting and endorsement [<xref ref-type="bibr" rid="scirp.127077-ref49">49</xref>] . This implies that the application of stem cells does not only diminish the cost of pharmaceutical drug discovery but also upsurges the prospect of spotting primes with a target or pathway noteworthy to the disease diagnosis.</p><p>It is also important to note that stem cells from different biological components are not alike [<xref ref-type="bibr" rid="scirp.127077-ref50">50</xref>] , and in vitro breeding where the stem cells are delivered with growing features is different from the small environment in which stem cells exist in the living system [<xref ref-type="bibr" rid="scirp.127077-ref51">51</xref>] . This means that stem cells have a more lethargic cell progression than their precursor cells in vivo, so the grade of the warmth of details resultant in a test tube or dish may vary from that of the living system [<xref ref-type="bibr" rid="scirp.127077-ref52">52</xref>] .</p></sec><sec id="s3_4"><title>3.4. In Silico Approach in Drug Discovery and Design</title><p>The use of the principle of mathematics and computer science application in biology has proven effective over the years, thereby triggering the expansion of the use of in silico approach. In silico (commonly called bioinformatics) denotes the use of computers or computer simulations to perform biological findings. Its practicality in biomedical sciences has additional worth to drug discovery study at the biotic level [<xref ref-type="bibr" rid="scirp.127077-ref53">53</xref>] [<xref ref-type="bibr" rid="scirp.127077-ref54">54</xref>] . Consequently, the computer approach is significant in cogent drug formulation, which principally depends on the prevailing biotic and pharmaceutical properties of ligands [<xref ref-type="bibr" rid="scirp.127077-ref55">55</xref>] . A sequence of ligands by such assets is vetted for the variety of the most feasible candidates. In silico approach is computer-based on the in vivo technique and their understanding is based on both mathematics and computations. In these techniques, mathematical means can be adopted to outline the integer of drug recipes in data screening, this will diminish the amount of pilot investigation in the order of tens of thousands of likely alignments. The result may perhaps be subjugated to the proof of identity of a prosperous drove-out drug amalgamation and the foremost syndrome subsidizing pathways. Computational scrutiny can now examine the amalgamated structures accompanying the host mechanisms, consistently the pathological pathways, to reserve therapeutic methods using equivalent models. A simulation is then run to definite considerations such as competencies, toxicities, and other side effects of the drugs in the handling of diseases from a system perception [<xref ref-type="bibr" rid="scirp.127077-ref56">56</xref>] .</p><p>Typical illustrations are selection models called medicinal algorithmic combinational screens, and measurable confirmation action affiliation of herbal formulae. In this method, the network-constructed biological computational approach is smeared by mathematical models demonstrating the biological pathways which govern the sophisticated level of cellular special effects in multi- target drugs. Also, the unified network target-based identification of the multicomponent synergy model, which relates drugs to their molecular targets [<xref ref-type="bibr" rid="scirp.127077-ref57">57</xref>] , emphasizes its presentation as a data-modeling practice.</p><p>The efficacy of the in-silico techniques has auxiliary enriched the recognition of the hazardous properties of drug substances [<xref ref-type="bibr" rid="scirp.127077-ref58">58</xref>] . The in silico system has also lengthy the prospects of drug repurposing by combined networks [<xref ref-type="bibr" rid="scirp.127077-ref59">59</xref>] [<xref ref-type="bibr" rid="scirp.127077-ref60">60</xref>] . This routine scrutinizes the genomic dissimilarities that give to different reactions to drugs for precision medicine use and the forecast of disease proneness [<xref ref-type="bibr" rid="scirp.127077-ref61">61</xref>] .</p><p>There are different approaches to in silico model of drug discovery, among which are genomics, proteomics, metabolomics, and much more with the most prominent one being molecular docking. Molecular docking is the use of the computational model for the prediction of ligands-target confirmation; of which ligands can be a small molecule or peptide synthesis from either plant, microbes, or animal while the target can be a protein or nucleic acid whose activity is paramount for the survival of a disease with having beneficial effect to the host or not evenly distributed throughout the living system. Although, because of the advances in silico analysis of drugs, several web servers are employed for the prediction of pharmacokinetics and drug-likeness proprietaries of a potential therapeutic agent. Also, a process called molecular dynamic stimulation is also employed to determine the selectivity and absorption potential of a promising drug candidate. <xref ref-type="fig" rid="fig2">Figure 2</xref> denotes the process involved in molecular docking, and <xref ref-type="table" rid="table2">Table 2</xref> gives a general overview of these techniques and their applications in drug discovery.</p><table-wrap id="table2" ><label><xref ref-type="table" rid="table2">Table 2</xref></label><caption><title> General overview of the applications of these techniques including their pros and cons</title></caption><table><tbody><thead><tr><th align="center" valign="middle" >Parameters</th><th align="center" valign="middle" >Stem cells as vitro models</th><th align="center" valign="middle" >In Silico Approach</th></tr></thead><tr><td align="center" valign="middle" >Definition</td><td align="center" valign="middle" >The use of stem cells in vitro to study drug responses and toxicity</td><td align="center" valign="middle" >The use of computer simulations to predict drug properties and interactions</td></tr><tr><td align="center" valign="middle" >Applications</td><td align="center" valign="middle" >Testing drug efficacy and toxicity, identifying drug targets and mechanisms of action, disease modeling, and drug screening</td><td align="center" valign="middle" >Predicting drug-target interactions, identifying drug candidates, optimizing drug properties, virtual screening, and molecular docking</td></tr><tr><td align="center" valign="middle" >Key Techniques</td><td align="center" valign="middle" >Differentiation of stem cells into specific cell types, microfluidics, gene editing, organoid culture, high-throughput screening, transcriptomics, and proteomics</td><td align="center" valign="middle" >Molecular docking, molecular dynamics simulation, virtual screening, ligand-based and structure-based drug design</td></tr><tr><td align="center" valign="middle" >Pros</td><td align="center" valign="middle" >More physiologically relevant models, potential for personalized medicine, and ability to model complex diseases</td><td align="center" valign="middle" >High throughput, cost-effective, allows for the exploration of large chemical space, no need for physical samples, and the ability to predict drug properties and interactions</td></tr><tr><td align="center" valign="middle" >Cons</td><td align="center" valign="middle" >Technical challenges and limitations, the potential for batch-to-batch variability, limited scalability and reproducibility, and ethical concerns related to the use of human embryos or fetal tissue</td><td align="center" valign="middle" >Limited accuracy and reliability, inability to account for all biological factors, lack of experimental validation, and inability to predict the toxicity and other adverse effects</td></tr><tr><td align="center" valign="middle" >References</td><td align="center" valign="middle" >[<xref ref-type="bibr" rid="scirp.127077-ref62">62</xref>] - [<xref ref-type="bibr" rid="scirp.127077-ref67">67</xref>]</td><td align="center" valign="middle" >[<xref ref-type="bibr" rid="scirp.127077-ref68">68</xref>] [<xref ref-type="bibr" rid="scirp.127077-ref69">69</xref>] [<xref ref-type="bibr" rid="scirp.127077-ref70">70</xref>] [<xref ref-type="bibr" rid="scirp.127077-ref71">71</xref>]</td></tr></tbody></table></table-wrap></sec></sec><sec id="s4"><title>4. Target Identification, Chemical Similarity Network and AI Integration in Drug Discovery</title><p>One of the newest trends in drug discovery is target identification, which is built on the discovery that a drug can muddle with other drugs and change its purpose by binding to the target accountable for the activity [<xref ref-type="bibr" rid="scirp.127077-ref72">72</xref>] . High throughput screening (HTS) is a popular target-based technique in which a large sum of compounds is uncovered for disease and decisions are made based on the chemical’s capacity to block the disease [<xref ref-type="bibr" rid="scirp.127077-ref73">73</xref>] . <xref ref-type="fig" rid="fig3">Figure 3</xref> shows an overview of the stages involved in drug development.</p><sec id="s4_1"><title>4.1. Approach Used in Chemical Similarity Network for Drug Discovery</title><p>Chemical similarity is a key perception in drug development that is utilized to invent compounds with comparable bioactivities centered on structural resemblances between two ligands [<xref ref-type="bibr" rid="scirp.127077-ref74">74</xref>] . A drug designer can build a series of structural</p><p>equivalents with superior pharmacological characteristics when a prime compound is revealed using a chemical screen. The chemical correspondence concept, which holds that if two compounds have analogous structures, they are probable to have equivalent bioactivities, is at the core of similarity-based drug discovery. While there are exceptions, the relationship between chemical structure and compound activity in medicinal chemistry is well known [<xref ref-type="bibr" rid="scirp.127077-ref75">75</xref>] . Consequently, the causal structural similarity between two compounds is a prerequisite aimed at match-built drug discovery. A visual inspection can quickly determine the similarity between two ligands at a basic level by finding shared practical groups, structural motifs, or substructures. On the other hand, human involvement is frequently subjective and unsuitable for large-scale examination. Therefore, a successful drug discovery exertion necessitates the use of computational methods for unprejudiced chemical connection assessment and a thorough database [<xref ref-type="bibr" rid="scirp.127077-ref76">76</xref>] .</p><p>More than a few computational chemical relationship search performances have been developed [<xref ref-type="bibr" rid="scirp.127077-ref74">74</xref>] [<xref ref-type="bibr" rid="scirp.127077-ref75">75</xref>] [<xref ref-type="bibr" rid="scirp.127077-ref76">76</xref>] . Chemical infrastructure impressions are the most often exploited method. By drawing common chemical motifs into twofold arrays known as structural keys, non-hashed structural fingerprints such as molecular access system (MACCS) keys or open babel fingerprints detect predetermined substructures or functional group patterns in a molecule. Each fragment is turned into a dualistic sequence of 0 and 1, representing the existence or absence of a precise substructure, to relate chemical relationships between two molecules. Chemical-muddled patterns, such as daylight fingerprints on the other hand, utilize paths in their hashing [<xref ref-type="bibr" rid="scirp.127077-ref74">74</xref>] .</p><p>The next step is to use a distance metric to measure chemical similarity when the chemical fingerprints have been resolute in a chemical hunt and the particles have been interpreted to acceptable data demonstrations. Some of the common distance measurements frequently used in chemoinformatics and bioinformatics to achieve this are Euclidean, and Mahalanobis metrics [<xref ref-type="bibr" rid="scirp.127077-ref77">77</xref>] . On the other hand, the Tanimoto index is the simplest and most direct distance metric in the instance of dual chemical impressions. In the range of 0 - 1, Tanimoto metrics compute the element of mutual bits among chemical prints. Even though there is no common Tanimoto index cutoff (Tc) for determining whether double fragments are satisfactorily alike, most chemical searches should begin with a Tc value of 0.7. Alternatively, depending on the total Tc score distribution, statistical metrics such as a Z-score can be generated [<xref ref-type="bibr" rid="scirp.127077-ref76">76</xref>] .</p><p>In addition, 3-dimensional chemical similarities prints have been engendered in addition to 2D prints. For structural correspondence assessment, 3D chemical connection patterns use 3D structural evidence from ligands such as molecular shape, pharmacophore points, or molecular interaction fields [<xref ref-type="bibr" rid="scirp.127077-ref75">75</xref>] . Even if 3D chemical match evaluations may stereotypically capture fundamental characteristics important for protein-ligand interaction, 3D arrangement systems are computationally expensive and often demand considerable optimization techniques to augment the coincided volume. Nonalignment approaches established on chemical descriptors such as GETAWAY or 3D-MoRSE descriptors, on the other hand, can be employed [<xref ref-type="bibr" rid="scirp.127077-ref78">78</xref>] . The 3D chemical descriptor can capture 3D ligand properties from 2D data, potentially reducing computing time. To prove 3D structural similarity, however, extensive post-validation may be required [<xref ref-type="bibr" rid="scirp.127077-ref77">77</xref>] .</p></sec><sec id="s4_2"><title>4.2. Future Recommendation: Encouraging the Integration of Artificial Intelligence and Biotechnology in Enhanced Drug Discovery</title><p>In the era of big data, the integration of artificial intelligence (AI) with biotechnology in drug discovery holds great promise [<xref ref-type="bibr" rid="scirp.127077-ref79">79</xref>] . By harnessing AI, hidden or meaningful patterns and relationships within complex biological systems can be discovered [<xref ref-type="bibr" rid="scirp.127077-ref80">80</xref>] . This will facilitate the analysis of genomic and proteomic data, enabling the identification of new therapeutic targets and the design of more effective drugs [<xref ref-type="bibr" rid="scirp.127077-ref81">81</xref>] . Through AI-driven predictive modeling, machine learning (ML) algorithms can be leveraged to analyze existing data on drug-target interactions, chemical structures, and biological activities. AI algorithms can also be utilized in two key areas: natural language processing (NLP) and virtual screening. In the context of NLP, AI algorithms can process and extract information from vast databases [<xref ref-type="bibr" rid="scirp.127077-ref82">82</xref>] . Additionally, AI algorithms can be employed in virtual screening to screen large databases of compounds [<xref ref-type="bibr" rid="scirp.127077-ref83">83</xref>] . This can help identify potential compounds that exhibit a high affinity for specific therapeutic targets. These analyses will help optimize drug design and the prediction of safe and therapeutically efficacious compounds. Embracing AI in biotechnology represents a transformative approach that accelerates the discovery of innovative therapeutic agents, providing researchers with powerful tools for precise and personalized treatment options.</p></sec></sec><sec id="s5"><title>5. Conclusion</title><p>Biotechnological models are a potent approach to drug discovery. Researchers are now using novel biotechnology models to discover new drugs for diseases. The discovery of new drugs involves the discovery of a protein that will improve and enhance treatment to better human lives. Some of the new drugs developed using this approach have proven to be effective and efficient in the treatment of some illnesses. The success of these drugs is a result of the novel technologies involved in their production. Thus, this novel technology and development will enable clinicians to administer various classes of drugs to attack the same illness. This review indicates that drug discovery in recent days is almost impossible without good modeling in biotechnology. Again, the integration of AI with biotechnology in drug discovery holds great promise. Therefore, biotechnological models for drug discovery and AI techniques should be encouraged and adopted by researchers and the drug manufacturing industries. Hence, the impact of biotechnological models in enhanced drug discovery cannot be overemphasized.</p></sec><sec id="s6"><title>Acknowledgements</title><p>The authors would like to thank the director and the entire executive team of Pan Africa Research Group (PARG) for their unique ideas in establishing a research platform where researchers from different backgrounds can collaborate to discuss revolutionary research. We also thank the entire team for their amazing contributions to the success of this review.</p></sec><sec id="s7"><title>Conflicts of Interest</title><p>The authors declare no conflicts of interest.</p></sec><sec id="s8"><title>Cite this paper</title><p>Suleiman, T.A., Francis, A.C., Ibrahim, A., Jonn-Joy, A.O., Adebiyi, E. and Anyimadu D.T. (2023) Biotechnological Drug Development―The Role of Proteins, Genes, In-Silico, and Stem Cells in Designing Models for Enhanced Drug Discovery. Open Access Library Journal, 10: e10520. https://doi.org/10.4236/oalib.1110520</p></sec></body><back><ref-list><title>References</title><ref id="scirp.127077-ref1"><label>1</label><mixed-citation publication-type="other" xlink:type="simple">Trosset, J.Y. and Carbonell, P. (2015) Synthetic Biology for Pharmaceutical Drug Discovery. Drug Design, Development, and Therapy, 9, 6285-6302.  
https://doi.org/10.2147/DDDT.S58049</mixed-citation></ref><ref id="scirp.127077-ref2"><label>2</label><mixed-citation publication-type="book" xlink:type="simple">Duelen, R., Corvelyn, M., Tortorella, I., Leonardi, L., Chai, Y.C. and Sampaolesi, M. (2019) Medicinal Biotechnology for Disease Modeling, Clinical Therapy, and Drug Discovery and Development. In: Matei, F. and Zirra, D., Eds., Introduction to Biotech Entrepreneurship: From Idea to Business, Springer, Berlin, 89-128.  
https://doi.org/10.1007/978-3-030-22141-6_5</mixed-citation></ref><ref id="scirp.127077-ref3"><label>3</label><mixed-citation publication-type="other" xlink:type="simple">Ho, R.J. (2013) Biotechnology and Biopharmaceuticals: Transforming Proteins and Genes into Drugs. John Wiley &amp; Sons, Hoboken.  
https://doi.org/10.1002/9781118660485</mixed-citation></ref><ref id="scirp.127077-ref4"><label>4</label><mixed-citation publication-type="book" xlink:type="simple">Miller, H.I. (2013) Biotechnology. In: Maloy, S. and Hughes, K., Eds., Brenner’s Encyclopedia of Genetics, 2nd Edition, Elsevier, Amsterdam, 346-348.  
https://doi.org/10.1016/B978-0-12-374984-0.00157-1</mixed-citation></ref><ref id="scirp.127077-ref5"><label>5</label><mixed-citation publication-type="other" xlink:type="simple">Gaisser, S. and Nusser, M. (2010) Stellenwert der Biotechnologie in der pharmazeutischen Wirkstoffentwicklung. Zeitschrift für Evidenz, Fortbildung und Qualit&amp;auml;t im Gesundheitswesen, 104, 732-737. https://doi.org/10.1016/j.zefq.2010.05.001</mixed-citation></ref><ref id="scirp.127077-ref6"><label>6</label><mixed-citation publication-type="other" xlink:type="simple">Neagu, M., Albulescu, R. and Tanase, C. (2015) Biotechnology Landscape in Cancer Drug Discovery. Future Science OA, 1, FSO12. https://doi.org/10.4155/fso.15.10</mixed-citation></ref><ref id="scirp.127077-ref7"><label>7</label><mixed-citation publication-type="other" xlink:type="simple">Ward, S.J. (2001) Impact of Genomics in Drug Discovery. BioTechniques, 31, 1-2.  
https://doi.org/10.2144/01313dd01</mixed-citation></ref><ref id="scirp.127077-ref8"><label>8</label><mixed-citation publication-type="other" xlink:type="simple">Kabadi, A., McDonnell, E., Frank, C.L. and Drowley, L. (2020) Applications of Functional Genomics for Drug Discovery. Sage Journals, 25, 823-842.  
https://doi.org/10.1177/2472555220902092</mixed-citation></ref><ref id="scirp.127077-ref9"><label>9</label><mixed-citation publication-type="other" xlink:type="simple">Peter, H. (2015) How Genome Sequencing Is Aiding Drug Research and Development.  
https://www.proclinical.com/blogs/2015-7/genome-sequencing-is-aiding-drug-research-and-development</mixed-citation></ref><ref id="scirp.127077-ref10"><label>10</label><mixed-citation publication-type="other" xlink:type="simple">Wang, L., McLeod, H.L. and Weinshilboum, R.M. (2011) Genomics and Drug Response. New England Journal of Medicine, 364, 1144-1153.  
https://doi.org/10.1056/NEJMra1010600</mixed-citation></ref><ref id="scirp.127077-ref11"><label>11</label><mixed-citation publication-type="other" xlink:type="simple">Lundstrom, K. (2011) Genomics and Drug Discovery. Future Medicinal Chemistry, 3, 1855-1858. https://doi.org/10.4155/fmc.11.140</mixed-citation></ref><ref id="scirp.127077-ref12"><label>12</label><mixed-citation publication-type="other" xlink:type="simple">Spreafico, R., Leah, B., Grossse, J., Virgin, H. and Telenti, A. (2020) Advances in Genomics for Drug Development. Genes, 11, 942.  
https://doi.org/10.3390/genes11080942</mixed-citation></ref><ref id="scirp.127077-ref13"><label>13</label><mixed-citation publication-type="other" xlink:type="simple">Neha, S. and Harikumar, L. (2013) Use of Genomics and Proteomics in Pharmaceutical Drug Discovery and Development: A Review. International Journal of Pharmacy and Pharmaceutical Sciences, 5, 24-28.</mixed-citation></ref><ref id="scirp.127077-ref14"><label>14</label><mixed-citation publication-type="other" xlink:type="simple">Bumol, T.F. and Watanabe, A.M. (2001) Genetic Information, Genomic Technologies, and the Future of Drug Discovery. JAMA, 285, 551-555.  
https://doi.org/10.1001/jama.285.5.551</mixed-citation></ref><ref id="scirp.127077-ref15"><label>15</label><mixed-citation publication-type="other" xlink:type="simple">Zhang, H.M., Nan, Z.R., Hui, G.Q., Liu, X.H. and Sun, Y. (2014) Application of Genomics and Proteomics in Drug Target Discovery. Genetics and Molecular Research: GMR, 13, 198-204. https://doi.org/10.4238/2014.January.10.11</mixed-citation></ref><ref id="scirp.127077-ref16"><label>16</label><mixed-citation publication-type="other" xlink:type="simple">Amiri-Dashatan, N., Koushki, M., Abbaszadeh, H.A., Rostami-Nejad, M. and Rezaei-Tavirani, M. (2018) Proteomics Applications in Health: Biomarker and Drug Discovery and Food Industry. Iranian Journal of Pharmaceutical Research: IJPR, 17, 1523.</mixed-citation></ref><ref id="scirp.127077-ref17"><label>17</label><mixed-citation publication-type="other" xlink:type="simple">Frantzi, M., Latosinska, A. and Mischak, H. (2019) Proteomics in Drug Development: The Dawn of a New Era? Proteomics-Clinical Applications, 13, Article ID: 1800087. https://doi.org/10.1002/prca.201800087</mixed-citation></ref><ref id="scirp.127077-ref18"><label>18</label><mixed-citation publication-type="other" xlink:type="simple">Jhanker, Y., Kadir, M., Khan, R. and Hasan, R. (2012) Proteomics in Drug Discovery, Journal of Applied Pharmaceutical Science, 2, 1-12.  
https://doi.org/10.7324/JAPS.2012.2801</mixed-citation></ref><ref id="scirp.127077-ref19"><label>19</label><mixed-citation publication-type="other" xlink:type="simple">Hewick, R.M., Lu, Z. and Wang, J.H. (2003) Proteomics in Drug Discovery. In: Advances in Protein Chemistry, Vol. 65, Elsevier, Amsterdam, 309-342.  
https://doi.org/10.1016/S0065-3233(03)01024-6</mixed-citation></ref><ref id="scirp.127077-ref20"><label>20</label><mixed-citation publication-type="other" xlink:type="simple">Walgran, J.L. and Thompson, D.C. (2004) Application of Proteomic Technologies in the Drug Development Process. Toxicology Letters, 149, 377-385.  
https://doi.org/10.1016/j.toxlet.2003.12.047</mixed-citation></ref><ref id="scirp.127077-ref21"><label>21</label><mixed-citation publication-type="other" xlink:type="simple">Gromova, M., Vaggelas, A., Dallmann, G. and Seimetz, D. (2020) Biomarkers: Opportunities and Challenges for Drug Development in the Current Regulatory Landscape. Biomarker Insights, 15. https://doi.org/10.1177/1177271920974652</mixed-citation></ref><ref id="scirp.127077-ref22"><label>22</label><mixed-citation publication-type="other" xlink:type="simple">Schomaker, S., Ramaiah, S., Khan, N. and Burkhardt, J. (2019) Safety Biomarker Applications in Drug Development. The Journal of Toxicological Sciences, 44, 225-235. https://doi.org/10.2131/jts.44.225</mixed-citation></ref><ref id="scirp.127077-ref23"><label>23</label><mixed-citation publication-type="other" xlink:type="simple">Shendure, J. and Ji, H. (2008) Next-Generation DNA Sequencing. Nature Biotechnology, 26, 1135-1145. https://doi.org/10.1038/nbt1486</mixed-citation></ref><ref id="scirp.127077-ref24"><label>24</label><mixed-citation publication-type="other" xlink:type="simple">McCarthy, M.I. and Hirschhorn, J.N. (2008) Genome-Wide Association Studies: Potential Next Steps on a Genetic Journey. Human Molecular Genetics, 17, R156-R165. https://doi.org/10.1093/hmg/ddn289</mixed-citation></ref><ref id="scirp.127077-ref25"><label>25</label><mixed-citation publication-type="other" xlink:type="simple">Altelaar, A.F., Munoz, J. and Heck, A.J. (2013) Next-Generation Proteomics: Towards an Integrative View of Proteome Dynamics. Nature Reviews Genetics, 14, 35-48. https://doi.org/10.1038/nrg3356</mixed-citation></ref><ref id="scirp.127077-ref26"><label>26</label><mixed-citation publication-type="other" xlink:type="simple">Aebersold, R. and Mann, M. (2016) Mass-Spectrometric Exploration of Proteome Structure and Function. Nature, 537, 347-355. https://doi.org/10.1038/nature19949</mixed-citation></ref><ref id="scirp.127077-ref27"><label>27</label><mixed-citation publication-type="book" xlink:type="simple">Aksu, B., Sezer, A.D., Yegen, G. and Kusu, L. (2016) QbD Implementation in Biotechnological Product Development Studies. In: Chen, T.S. and Chai, S.C., Eds., Special Topics in Drug Discovery, IntechOpen, London, 133-155.  
https://doi.org/10.5772/66296</mixed-citation></ref><ref id="scirp.127077-ref28"><label>28</label><mixed-citation publication-type="book" xlink:type="simple">Nayak, A.K., Ahmed, S.A., Beg, S., Tabish, M. and Hasnain, M.S. (2019) Application of Quality by Design for the Development of Biopharmaceuticals. In: Beg, S. and Hasnain, M.S., Eds., Pharmaceutical Quality by Design, Academic Press, Cambridge, 399-411. https://doi.org/10.1016/B978-0-12-815799-2.00019-8</mixed-citation></ref><ref id="scirp.127077-ref29"><label>29</label><mixed-citation publication-type="other" xlink:type="simple">Rathore, A.S. and Winkle, H. (2009) Quality by Design for Biopharmaceuticals. Nature Biotechnology, 27, 26-34. https://doi.org/10.1038/nbt0109-26</mixed-citation></ref><ref id="scirp.127077-ref30"><label>30</label><mixed-citation publication-type="other" xlink:type="simple">Varu, R.K. and Khanna, A. (2010) Opportunities and Challenges to Implementing the Quality by Design Approach in Generic Drug Development. Journal of Generic Medicines, 7, 60-73. https://doi.org/10.1057/jgm.2009.37</mixed-citation></ref><ref id="scirp.127077-ref31"><label>31</label><mixed-citation publication-type="other" xlink:type="simple">Rathore, A.S. (2009) Roadmap for Implementation of Quality by Design (QbD) for Biotechnology Products. Trends in Biotechnology, 27, 546-553.  
https://doi.org/10.1016/j.tibtech.2009.06.006</mixed-citation></ref><ref id="scirp.127077-ref32"><label>32</label><mixed-citation publication-type="other" xlink:type="simple">Tomba, E., Facco, P., Bezzo, F. and Barolo, M. (2013) Latent Variable Modeling to Assist the Implementation of Quality-by-Design Paradigms in Pharmaceutical Development and Manufacturing: A Review. International Journal of Pharmaceutics, 457, 283-297. https://doi.org/10.1016/j.ijpharm.2013.08.074</mixed-citation></ref><ref id="scirp.127077-ref33"><label>33</label><mixed-citation publication-type="other" xlink:type="simple">Yu, L.X. (2008) Pharmaceutical Quality by Design: Product and Process Development, Understanding, and Control. Pharmaceutical Research, 25, 781-791.  
https://doi.org/10.1007/s11095-007-9511-1</mixed-citation></ref><ref id="scirp.127077-ref34"><label>34</label><mixed-citation publication-type="other" xlink:type="simple">Yu, L.X., Amidon, G., Khan, M.A., Hoag, S.W., Polli, J., Raju, G.K. and Woodcock, J. (2014) Understanding Pharmaceutical Quality by Design. The AAPS Journal, 16, 771-783. https://doi.org/10.1208/s12248-014-9598-3</mixed-citation></ref><ref id="scirp.127077-ref35"><label>35</label><mixed-citation publication-type="other" xlink:type="simple">Thompson, R.A., Isin, E.M., Li, Y., Weaver, R., Weidolf, L., Wilson, I. and Kenna, J.G. (2011) Risk Assessment and Mitigation Strategies for Reactive Metabolites in Drug Discovery and Development. Chemical-Biological Interactions, 192, 65-71.  
https://doi.org/10.1016/j.cbi.2010.11.002</mixed-citation></ref><ref id="scirp.127077-ref36"><label>36</label><mixed-citation publication-type="other" xlink:type="simple">Zhang, X., Lionberger, R.A., Davit, B.M. and Yu, L.X. (2011) Utility of Physiologically Based Absorption Modeling in Implementing Quality by Design in Drug Development. The AAPS Journal, 13, 59-71.  
https://doi.org/10.1208/s12248-010-9250-9</mixed-citation></ref><ref id="scirp.127077-ref37"><label>37</label><mixed-citation publication-type="other" xlink:type="simple">Hu, L., Fawcett, J.P. and Gu, J. (2012) Protein Target Discovery of Drug and Its Reactive Intermediate Metabolite by Using Proteomic Strategy. Acta Pharmaceutica Sinica B, 2, 126-136. https://doi.org/10.1016/j.apsb.2012.02.001</mixed-citation></ref><ref id="scirp.127077-ref38"><label>38</label><mixed-citation publication-type="book" xlink:type="simple">Dimitrov, D.S. (2012) Therapeutic Proteins. In: Voynov, V. and Caravella, J.A., Eds., Therapeutic Proteins Methods and Protocols, Vol. 899, Springer, Berlin, 1-26.  
https://doi.org/10.1007/978-1-61779-921-1_1</mixed-citation></ref><ref id="scirp.127077-ref39"><label>39</label><mixed-citation publication-type="other" xlink:type="simple">Zheng, J., Mehl, J., Zhu, Y., Xin, B. and Olah, T. (2014) Application and Challenges in Using LC-MS Assays for Absolute Quantitative Analysis of Therapeutic Proteins in Drug Discovery. Bioanalysis, 6, 859-879. https://doi.org/10.4155/bio.14.36</mixed-citation></ref><ref id="scirp.127077-ref40"><label>40</label><mixed-citation publication-type="other" xlink:type="simple">Daub, H., Godl, K., Brehmer, D., Klebl, B. and Müller, G. (2004) Evaluation of Kinase Inhibitor Selectivity by Chemical Proteomics. Assay and Drug Development Technologies, 2, 215-224. https://doi.org/10.1089/154065804323056558</mixed-citation></ref><ref id="scirp.127077-ref41"><label>41</label><mixed-citation publication-type="other" xlink:type="simple">Staker, B.L., Buchko, G.W. and Myler, P.J. (2015) Recent Contributions of Structure-Based Drug Design to the Development of Antibacterial Compounds. Current Opinion in Microbiology, 27, 133-138. https://doi.org/10.1016/j.mib.2015.09.003</mixed-citation></ref><ref id="scirp.127077-ref42"><label>42</label><mixed-citation publication-type="other" xlink:type="simple">Moellering, R.E. and Cravatt, B.F. (2012) How Chemoproteomics Can Enable Drug Discovery and Development. Chemistry &amp; Biology, 19, 11-22.  
https://doi.org/10.1016/j.chembiol.2012.01.001</mixed-citation></ref><ref id="scirp.127077-ref43"><label>43</label><mixed-citation publication-type="other" xlink:type="simple">Debouck, C. (2009) Integrating Genomics across Drug Discovery and Development. Toxicology Letters, 186, 9-12. https://doi.org/10.1016/j.toxlet.2008.09.011</mixed-citation></ref><ref id="scirp.127077-ref44"><label>44</label><mixed-citation publication-type="book" xlink:type="simple">Bahadduri, P.M., Polli, J.E., Swaan, P.W. and Ekins, S. (2010) Targeting Drug Transporters-Combining in Silico and in Vitro Approaches to Predict in Vivo. In: Yan, Q., Ed., Membrane Transporters in Drug Discovery and Development, Springer, Berlin, 65-103. https://doi.org/10.1007/978-1-60761-700-6_4</mixed-citation></ref><ref id="scirp.127077-ref45"><label>45</label><mixed-citation publication-type="other" xlink:type="simple">Gomez-Lechon, M.J., Lahoz, A., Gombau, L., Castell, J.V. and Donato, M.T. (2010) In Vitro Evaluation of Potential Hepatotoxicity Induced by Drugs. Current Pharmaceutical Design, 16, 1963-1977. https://doi.org/10.2174/138161210791208910</mixed-citation></ref><ref id="scirp.127077-ref46"><label>46</label><mixed-citation publication-type="other" xlink:type="simple">Vandana, U.K., Rajkumari, J., Singha, L.P., Satish, L., Alavilli, H., Sudheer, P.D. and Pandey, P. (2021) The Endophytic Microbiome as a Hotspot of Synergistic Interactions, with Prospects of Plant Growth Promotion. Biology, 10, Article No. 101.  
https://doi.org/10.3390/biology10020101</mixed-citation></ref><ref id="scirp.127077-ref47"><label>47</label><mixed-citation publication-type="other" xlink:type="simple">Risue&amp;ntilde;o, I., Valencia, L., Jorcano, J.L. and Velasco, D. (2021) Skin-on-a-Chip Models: General Overview and Future Perspectives. APL Bioengineering, 5, Article ID: 030901. https://doi.org/10.1063/5.0046376</mixed-citation></ref><ref id="scirp.127077-ref48"><label>48</label><mixed-citation publication-type="other" xlink:type="simple">Van Vliet, P., Sluijter, J.P., Doevendans, P.A. and Goumans, M.J. (2007) Isolation and Expansion of Resident Cardiac Progenitor Cells. Expert Review of Cardiovascular Therapy, 5, 33-43. https://doi.org/10.1586/14779072.5.1.33</mixed-citation></ref><ref id="scirp.127077-ref49"><label>49</label><mixed-citation publication-type="other" xlink:type="simple">Nirmalanandhan, V.S. and Sittampalam, G.S. (2009) Stem Cells in Drug Discovery, Tissue Engineering, and Regenerative Medicine: Emerging Opportunities and Challenges. Journal of Biomolecular Screening, 14, 755-768.  
https://doi.org/10.1177/1087057109336591</mixed-citation></ref><ref id="scirp.127077-ref50"><label>50</label><mixed-citation publication-type="other" xlink:type="simple">Mimeault, M. and Batra, S.K. (2006) Concise Review: Recent Advances on the Significance of Stem Cells in Tissue Regeneration and Cancer Therapies. Stem Cells, 24, 2319-2345. https://doi.org/10.1634/stemcells.2006-0066</mixed-citation></ref><ref id="scirp.127077-ref51"><label>51</label><mixed-citation publication-type="other" xlink:type="simple">Keung, A.J., Kumar, S. and Schaffer, D.V. (2010) Presentation Counts: Microenvironmental Regulation of Stem Cells by Biophysical and Material Cues. Annual Review of Cell and Developmental Biology, 26, 533-556.  
https://doi.org/10.1146/annurev-cellbio-100109-104042</mixed-citation></ref><ref id="scirp.127077-ref52"><label>52</label><mixed-citation publication-type="other" xlink:type="simple">Augello, A., Kurth, T.B. and De Bari, C. (2010) Mesenchymal Stem Cells: A Perspective from in Vitro Cultures to in Vivo Migration and Niches. European Cells and Materials, 20, e33. https://doi.org/10.22203/eCM.v020a11</mixed-citation></ref><ref id="scirp.127077-ref53"><label>53</label><mixed-citation publication-type="other" xlink:type="simple">Hunter, P.J. and Borg, T.K. (2003) Integration from Proteins to Organs: The Physiome Project. Nature Reviews Molecular Cell Biology, 4, 237-243.  
https://doi.org/10.1038/nrm1054</mixed-citation></ref><ref id="scirp.127077-ref54"><label>54</label><mixed-citation publication-type="other" xlink:type="simple">Noble, D. (2002) Modeling the Heart—From Genes to Cells to the Whole Organ. Science, 295, 1678-1682. https://doi.org/10.1126/science.1069881</mixed-citation></ref><ref id="scirp.127077-ref55"><label>55</label><mixed-citation publication-type="other" xlink:type="simple">Bassingthwaighte, J.B. and Vinnakota, K.C. (2004) The Computational Integrated Myocyte: A View into the Virtual Heart. Annals of the New York Academy of Sciences, 1015, 391-404. https://doi.org/10.1196/annals.1302.034</mixed-citation></ref><ref id="scirp.127077-ref56"><label>56</label><mixed-citation publication-type="other" xlink:type="simple">Wang, F.Y. and Wong, P.K. (2013) Intelligent Systems and Technology for Integrative and Predictive Medicine: An ACP Approach. ACM Transactions on Intelligent Systems and Technology (TIST), 4, 1-6. https://doi.org/10.1145/2438653.2438667</mixed-citation></ref><ref id="scirp.127077-ref57"><label>57</label><mixed-citation publication-type="other" xlink:type="simple">Li, S., Zhang, B. and Zhang, N. (2011) Network Target for Screening Synergistic Drug Combinations with Application to Traditional Chinese Medicine. BMC Systems Biology, 5, 1-13. https://doi.org/10.1186/1752-0509-5-S1-S10</mixed-citation></ref><ref id="scirp.127077-ref58"><label>58</label><mixed-citation publication-type="other" xlink:type="simple">Kuhn, M., Campillos, M., Letunic, I., Jensen, L.J. and Bork, P. (2010) A Side Effect Resource to Capture Phenotypic Effects of Drugs. Molecular Systems Biology, 6, 343. https://doi.org/10.1038/msb.2009.98</mixed-citation></ref><ref id="scirp.127077-ref59"><label>59</label><mixed-citation publication-type="other" xlink:type="simple">Ekins, S., Williams, A.J., Krasowski, M.D. and Freundlich, J.S. (2011) In Silico Repositioning of Approved Drugs for Rare and Neglected Diseases. Drug Discovery Today, 16, 298-310. https://doi.org/10.1016/j.drudis.2011.02.016</mixed-citation></ref><ref id="scirp.127077-ref60"><label>60</label><mixed-citation publication-type="other" xlink:type="simple">Mendrick, D.L. (2011) Transcriptional Profiling to Identify Biomarkers of Disease and Drug Response. Pharmacogenomics, 12, 235-249.  
https://doi.org/10.2217/pgs.10.184</mixed-citation></ref><ref id="scirp.127077-ref61"><label>61</label><mixed-citation publication-type="other" xlink:type="simple">Mah, J.T., Low, E.S. and Lee, E. (2011) In Silico SNP Analysis and Bioinformatics Tools: A Review of the State of the Art to Aid Drug Discovery. Drug Discovery Today, 16, 800-809. https://doi.org/10.1016/j.drudis.2011.07.005</mixed-citation></ref><ref id="scirp.127077-ref62"><label>62</label><mixed-citation publication-type="other" xlink:type="simple">Liu, Y., Wang, L., Kikuiri, T., Akiyama, K., Chen, C., Xu, X. and Shi, S. (2020) Mesenchymal Stem Cell-Based Tissue Regeneration Is Governed by Recipient T Lymphocytes via IFN-γ and TNF-α. Nature Medicine, 24, 1434-1442.</mixed-citation></ref><ref id="scirp.127077-ref63"><label>63</label><mixed-citation publication-type="other" xlink:type="simple">Bhatia, S.N. and Ingber, D.E. (2014) Microfluidic Organs-on-Chips. Nature Biotechnology, 32, 760-772. https://doi.org/10.1038/nbt.2989</mixed-citation></ref><ref id="scirp.127077-ref64"><label>64</label><mixed-citation publication-type="other" xlink:type="simple">Murphy, S.V. and Atala, A. (2017) 3D Bioprinting of Tissues and Organs. Nature Biotechnology, 35, 213-222.</mixed-citation></ref><ref id="scirp.127077-ref65"><label>65</label><mixed-citation publication-type="other" xlink:type="simple">Clevers, H. (2016) Modeling Development and Disease with Organoids. Cell, 165, 1586-1597. https://doi.org/10.1016/j.cell.2016.05.082</mixed-citation></ref><ref id="scirp.127077-ref66"><label>66</label><mixed-citation publication-type="other" xlink:type="simple">Abaci, H.E., Shen, Y.I. and Wu, J.C. (2015) In Vivo Imaging of Embryonic Stem Cells Reveals Patterns of Survival and Immune Rejection Following Transplantation. Stem Cells and Development, 24, 321-330.</mixed-citation></ref><ref id="scirp.127077-ref67"><label>67</label><mixed-citation publication-type="other" xlink:type="simple">Takahashi, K., Tanabe, K., Ohnuki, M., Narita, M., Ichisaka, T., Tomoda, K. and Yamanaka, S. (2007) Induction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined Factors. Cell, 131, 861-872.  
https://doi.org/10.1016/j.cell.2007.11.019</mixed-citation></ref><ref id="scirp.127077-ref68"><label>68</label><mixed-citation publication-type="other" xlink:type="simple">Walters, W.P. and Murcko, M.A. (2002) Prediction of “Drug-Likeness”. Advanced Drug Delivery Reviews, 54, 255-271.  
https://doi.org/10.1016/S0169-409X(02)00003-0</mixed-citation></ref><ref id="scirp.127077-ref69"><label>69</label><mixed-citation publication-type="other" xlink:type="simple">Lavecchia, A. and Di Giovanni, C. (2013) Virtual Screening Strategies in Drug Discovery: A Critical Review. Current Medicinal Chemistry, 20, 2839-2860.  
https://doi.org/10.2174/09298673113209990001</mixed-citation></ref><ref id="scirp.127077-ref70"><label>70</label><mixed-citation publication-type="other" xlink:type="simple">Cheng, F., Li, W., Wu, Z., Wang, X., Zhang, C., Li, J. and Tang, Y. (2013) Prediction of Polypharmacological Profiles of Drugs by the Integration of Chemical, Side Effect, and Therapeutic Space. Journal of Chemical Information and Modeling, 53, 753-762. https://doi.org/10.1021/ci400010x</mixed-citation></ref><ref id="scirp.127077-ref71"><label>71</label><mixed-citation publication-type="other" xlink:type="simple">Kitchen, D.B., Decornez, H., Furr, J.R. and Bajorath, J. (2004) Docking and Scoring in Virtual Screening for Drug Discovery: Methods and Applications. Nature Reviews Drug Discovery, 3, 935-949. https://doi.org/10.1038/nrd1549</mixed-citation></ref><ref id="scirp.127077-ref72"><label>72</label><mixed-citation publication-type="other" xlink:type="simple">Smith, A., Ammar, R., Nislow, C., Giaever, G. (2010) A Survey of Yeast Genomic Assays for Drug and Target Discovery. Pharmacology &amp; Therapeutics, 127, 156-164. https://doi.org/10.1016/j.pharmthera.2010.04.012</mixed-citation></ref><ref id="scirp.127077-ref73"><label>73</label><mixed-citation publication-type="other" xlink:type="simple">Nermin, P.K., Murodzhon, A. and Murat, C. (2014) A Drug Similarity Network for Understanding Drug Mechanism of Action. Journal of Bioinformatics and Computational Biology, 12, Article ID: 1441007.  
https://doi.org/10.1142/S0219720014410078</mixed-citation></ref><ref id="scirp.127077-ref74"><label>74</label><mixed-citation publication-type="other" xlink:type="simple">Yan, X., Liao, C., Liu, Z., Hagler, A.T., Gu, Q. and Xu, J. (2015) Chemical Structure Similarity Search for Ligand-Based Virtual Screening: Methods and Computational Resources. Current Drug Targets, 16, 1580-1585.</mixed-citation></ref><ref id="scirp.127077-ref75"><label>75</label><mixed-citation publication-type="other" xlink:type="simple">Maggiora, G., Vogt, M., Stumpfe, D. and Bajorath, J. (2014) Molecular Similarity in Medicinal Chemistry. Journal of Medicinal Chemistry, 57, 3186-3204.  
https://doi.org/10.1021/jm401411z</mixed-citation></ref><ref id="scirp.127077-ref76"><label>76</label><mixed-citation publication-type="other" xlink:type="simple">Faulon, J.L. and Bender, A. (2010) Handbook of Chemoinformatics Algorithms. CRC Press, Boca Raton. https://doi.org/10.1201/9781420082999</mixed-citation></ref><ref id="scirp.127077-ref77"><label>77</label><mixed-citation publication-type="other" xlink:type="simple">Lee, K. (2010) Statistical Bioinformatics: A Guide for Life and Biomedical Science Researchers. Wiley-Blackwell, Hoboken.</mixed-citation></ref><ref id="scirp.127077-ref78"><label>78</label><mixed-citation publication-type="other" xlink:type="simple">Devinyak, O., Havrylyuk, D. and Lesyk, R. (2014) 3D-MoRSE Descriptors Explained. Journal of Molecular Graphics and Modelling, 54, 194-203.  
https://doi.org/10.1016/j.jmgm.2014.10.006</mixed-citation></ref><ref id="scirp.127077-ref79"><label>79</label><mixed-citation publication-type="other" xlink:type="simple">Holzinger, A., Keiblinger, K., Holub, P., Zatloukal, K. and Müller, H. (2023) AI for Life: Trends in Artificial Intelligence for Biotechnology. New Biotechnology, 74, 16-24. https://doi.org/10.1016/j.nbt.2023.02.001</mixed-citation></ref><ref id="scirp.127077-ref80"><label>80</label><mixed-citation publication-type="other" xlink:type="simple">Suleiman, T.A., Tolulope, A.M., Wuraola, F.O., Olorunfemi, R., Kasali, W.A., Okorocha, B.O., Dirisu, C. and Njoku, P.C. (2023) Overview of Cancer Management—The Role of Medical Imaging and Machine Learning Techniques in Early Detection of Cancer: Prospects, Challenges, and Future Directions. Open Access Library Journal, 10, e10014. https://doi.org/10.4236/oalib.1110014</mixed-citation></ref><ref id="scirp.127077-ref81"><label>81</label><mixed-citation publication-type="other" xlink:type="simple">Gupta, R., Srivastava, D., Sahu, M., Tiwari, S., Ambasta, R.K. and Kumar, P. (2021) Artificial Intelligence to Deep Learning: Machine Intelligence Approach for Drug Discovery. Molecular Diversity, 25, 1315-1360.  
https://doi.org/10.1007/s11030-021-10217-3</mixed-citation></ref><ref id="scirp.127077-ref82"><label>82</label><mixed-citation publication-type="other" xlink:type="simple">Saldívar-González, F.I., Aldas-Bulos, V.D., Medina-Franco, J.L. and Plisson, F. (2022) Natural Product Drug Discovery in the Artificial Intelligence Era. Chemical Science, 13, 1526-1546. https://doi.org/10.1039/D1SC04471K</mixed-citation></ref><ref id="scirp.127077-ref83"><label>83</label><mixed-citation publication-type="other" xlink:type="simple">Tripathi, A., Misra, K., Dhanuka, R. and Singh, J.P. (2022) Artificial Intelligence in Accelerating Drug Discovery and Development. Recent Patents on Biotechnology, 17, 9-23. https://doi.org/10.2174/1872208316666220802151129</mixed-citation></ref></ref-list></back></article>