Novel compounds show promise in fighting COVID-19
· News-MedicalDespite 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 designed to identify the important binding regions that a drug candidate compound would interact with. Using their drug discovery process, Salvino and the team identified a novel series of Mpro inhibitors with greater selectivity -; that is, more reliable at producing an inhibitory effect -; than the existing Mpro inhibitor for COVID-19 on the market.
The group's novel compounds successfully inhibited viral replication in vitro against three different COVID variants, including within lung tissue. The compound also synergized (i.e., achieved greater-than-the-sum-of-its-parts strength) with other existing antivirals in fighting the virus. In the preclinical testing, no apparent toxicities were observed -; a positive indication of the compound's safety.
"As we continue to refine the chemistry through further testing and optimization, we look forward to achieving improved potency in anti-coronaviral therapies."
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