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Potent Inhibitors of SARS-CoV-2 Main Protease

Using DNA-encoded chemical library technology to discover potent inhibitors of the SARS CoV-2 Mpro

Published: 5th July 2022
Potent Inhibitors of SARS-CoV-2 Main Protease


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
  • Figure 1: Crystal structure of Mpro in complex with CDD-1713

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.

  • Provisional patent application filed July 2021
IP Status
  • Patent application submitted
  • Licensing
  • Commercial partner
  • Development partner