TITLE:
Development of a Targeted Drug Delivery System for the Treatment of SARS-CoV-2
AUTHORS:
Sahil Sood
KEYWORDS:
Covid-19, SARS-CoV-2, PLGA, Drug Delivery, Chemotaxis
JOURNAL NAME:
Journal of Biosciences and Medicines,
Vol.10 No.10,
October
10,
2022
ABSTRACT: SARS-CoV-2 has triggered a public health outbreak across the world, resulting in almost 5 million deaths as of January 2022. The arrival of vaccines has provided temporary relief, but these vaccines target the spike protein, which is highly prone to mutation, making it impossible to develop a long-term cure for the coronavirus. As such, there is an urgent need for site-specific inhibition of the virus in the respiratory tract, as well as targeting the internal proteins of the virus itself. Past literature has identified 3CLpro and PLpro as enzymes essential to the replication of the virus, as they assemble almost the entirety of the viral genome; as such, inhibiting the activity of these enzymes can stymie the spread of the virus. This project proposes the use of inhaled drug delivery to inhibit Covid-19 by synthesizing a formulation that can travel directly to the lungs via inhalation. In order to streamline synthesis, existing FDA-approved drugs were analyzed using computational docking software and in vitro assays for inhibitory activity against these two enzymes. High-performing drugs were then encapsulated in PLGA nanoparticles to synthesize a drug delivery system, which was tested and characterized in vitro. Furthermore, in an effort to improve this drug delivery system relative to other drug delivery systems, the use of enzyme nanomotors was explored as a way to increase the accuracy of delivery by using computational simulations that mimicked conditions in the human body to model the velocity and trajectory of the nanomotors.