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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

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