Back to School: How biopharma can reboot drug development. Access exclusive analysis here

BioCentury is providing this content for free given the urgent need for information about the coronavirus crisis. Further analysis can be found in our COVID-19 Resource Center. For more, sign up for our daily email.
1013 data byte
BioCentury & Infogram

Product Development

Data Bytes: coronavirus-targeted small molecules

Oct 13, 2020 | 10:40 PM GMT

The SARS-CoV-2 protease is the top target for small molecule COVID-19 candidates developed with a coronavirus infection as their original indication, of which only a handful have entered the clinic.

Out of the 281 small molecule candidates in BioCentury’s COVID-19 portal, 22 were developed with SARS-CoV-2, SARS-CoV or another coronavirus as the intended target. 

Three of these compounds are in the clinic.

MK-4482, a nucleoside analog from Merck & Co. Inc. (NYSE:MRK), Emory University and Ridgeback Biotherapeutics L.P.,  inhibits the activity of the viral RNA-dependent RNA polymerase, and is in Phase II testing to treat hospitalized COVID-19 patients. 

RBT-9 from Renibus Therapeutics Inc., which inhibits viral replication via an undetermined target, is in Phase II testing for prevention of COVID-19 in high-risk individuals.

PF-07304814 from Pfizer Inc. (NYSE:PFE), which inhibits the protease SARS-CoV-2 3CLpro, is in Phase I testing for hospitalized COVID-19 patients.

At least five other companies have SARS-CoV-2 3CLpro inhibitors in preclinical development: Anivive Lifesciences Inc., Cocrystal Pharma Inc. (NASDAQ:COCP), Insilico Medicine Inc., Pardes Biosciences Inc. and Sosei Group Corp. (Tokyo:4565). 

In a conversation with BioCentury, Novartis Institutes for BioMedical Research (NIBR) president Jay Bradner said the similarity between the proteases of SARS-CoV-2 and SARS-CoV represented a missed opportunity; if coronavirus protease research had been sustained in the wake of the SARS epidemic, the world would have had inhibitors ready to deploy against COVID-19 (see “Hard Lessons and Hope in Coronavirus Research”).

Among the seven compounds with undisclosed targets, four are categorized as antivirals, two as immunosuppresants, and one as a metabolic modulator.

Cathepsin L (CTSL)
eIF4E – Eukaryotic translation initiation factor 4E
SARS-CoV-2 3CLpro (SARS-CoV-2 NSP5; SARS-CoV-2 Mpro; SARS-CoV-2 main protease) – SARS-CoV-2 3C-like protease
SARS-CoV-2 AH – SARS-CoV-2 frameshift attenuator hairpin
SARS-CoV-2 S – SARS-CoV-2 spike protein

Trial Subscription

Get a two-week free trial subscription to BioCentury


Article Purchase

This article may not be distributed to non-subscribers