New research from The Wistar Institute's Salvino lab -; led by professor Joseph Salvino, Ph.D. -; has identified a novel series of SARS-CoV-2 Mpro inhibitors that may lead to potential new COVID-19 treatments that, according to preclinical testing, effectively inhibits COVID-19 and synergizes with existing anti-COVID therapies.
Their new discovery is detailed in the paper, "Design of novel and highly selective SARS-CoV-2 main protease inhibitors," published in the journal Antimicrobial Agents and Chemotherapy. Despite effective vaccines approved for use worldwide, COVID-19 continues to contribute to mortality and morbidity -; an issue compounded by the problems of vaccine & therapy access. However, the existing drug designs in use for COVID-19 therapy lend themselves to drug interactions and the risk of incomplete viral inhibition.
To address this problem, Salvino -; a medicinal chemist at Wistar -; led a drug discovery team with the goal of improving upon the existing Mpro inhibitor design, an approach to viral therapy that seeks to prevent both viral replication and mutation -based drug resistance by targeting a component of the virus that regulates its ability to spread. And because Mpro is not an easy-to-mutate biological feature like a spike protein, inhibiting Mpro can help retain antiviral effectiveness even between different variations. The team used a drug discovery technique that applied an "acyloxymethyl ketone electrophilic warhead" -; in essence, a molecule desig.
