Potent Inhibitors of SARS-CoV-2 Main Protease

Baylor College of Medicine Background
Both industry and academia are pursuing drugs for treatment of COVID-19

US govt committed to $3B investment for development of antiviral drugs
Gilead’s Remdesivir is approved or has emergency authorization in over 50 countries; however, clinical trial results are mixed
Merck’s molnupiravir antiviral drug is currently under review by the FDA; data is also uncertain
Pfizer’s novel COVID-19 protease inhibitor is in Phase II/III trials

Continued need for an effective COVID antiviral drug

$6B market estimate for U.S. market of antiviral
Potentially 18M US cases per year if the virus becomes endemic
Worldwide, there have been over 270M COVID-19 cases and over 5M deaths, including ~800K deaths in the US

Technology Overview
The Center for Drug Discovery (CDD) at Baylor College of Medicine (BCM) has constructed over 60 DNA Encoded Chemical Libraries (DECLs) that encode 6 billion compounds and has optimized DNA-encoded library screens, informatics, and follow-up off-DNA chemical resynthesis to facilitate a rapid pipeline from recombinant protein to potent hit.
BCM innovators have successfully identified low nanomolar covalent and non-covalent inhibitors of SARS-CoV-2 Mpro and generated co-crystals of SARS-CoV-2 Mpro with these small molecule drug-like inhibitors.

Evaluated viral inhibition of Mpro inhibitors, using a live strain of SARS-CoV-2 virus
Selected compounds successfully reduced cell death in a dose-dependent manner indicating that virus replication was stopped

Stage of Development
Identified small molecule lead compounds currently being tested using in vivo transgenic mouse models.
Further Details
Treating COVID-19 & other potential Coronaviruses
Seeking licensure and/or commercial partner for further clinical dev.

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