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Old 9th November 2021, 09:40 AM   #288
Chris_Halkides
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Pfizer's reversible, covalent protease inhibitor

C&E News wrote, "PF-07321332 was developed from scratch during the current pandemic. It’s a reversible covalent inhibitor that reacts with one of the main protease’s cysteine residues."

At In the Pipeline Derek Lowe wrote, "Let’s think about some of the implications: first, an utterly obvious question is whether molnupiravir and Paxlovid can be combined into a cocktail regimen, as we have seen for other viral diseases like HIV and Hepatitis C. Those are by far the most successful small-molecule antiviral treatments ever discovered, and there seems to be no reason why this situation wouldn’t be similar."

I don't have as much information as I would like, but it sounds as if the main protease is related to papain, and the targeted cysteine may be the nucleophile in the catalytic cycle. The warhead is the nitrile group. See for example, this paper.
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Last edited by Chris_Halkides; 9th November 2021 at 09:58 AM.
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