Differential inhibition of intra- and inter-molecular protease cleavages by antiviral compounds.

Autor:	Doherty JS; Department of Genetics, Stanford University, Palo Alto, California, USA., Kirkegaard K; Department of Genetics, Stanford University, Palo Alto, California, USA.; Department of Microbiology and Immunology, Stanford University, Palo Alto, California, USA.
Jazyk:	angličtina
Zdroj:	Journal of virology [J Virol] 2023 Dec 21; Vol. 97 (12), pp. e0092823. Date of Electronic Publication: 2023 Dec 04.
DOI:	10.1128/jvi.00928-23
Abstrakt:	Importance: Most protease-targeted antiviral development evaluates the ability of small molecules to inhibit the cleavage of artificial substrates. However, before they can cleave any other substrates, viral proteases need to cleave themselves out of the viral polyprotein in which they have been translated. This can occur either intra- or inter-molecularly. Whether this process occurs intra- or inter-molecularly has implications for the potential for precursors to accumulate and for the effectiveness of antiviral drugs. We argue that evaluating candidate antivirals for their ability to block these cleavages is vital to drug development because the buildup of uncleaved precursors can be inhibitory to the virus and potentially suppress the selection of drug-resistant variants. Competing Interests: The authors declare no conflict of interest.
Databáze:	MEDLINE
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