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Article

Divergent resistance pathways amongst SARS-CoV-2 PLpro inhibitors highlight the need for scaffold diversity.

PLoS pathogens - 1 Sept 2025

Wu Xinyu, Devine Shane M, Go Margareta, Nguyen Julie V, Lu Bernadine G C, Loi Katie, Kuchel Nathan W, Lowes Kym N, Mitchell Jeffrey P, Lessene Guillaume, Komander David, Call Matthew E, Call Melissa J

Abstract excerpt

Drug-escape, where a target evolves to escape inhibition from a drug, has the potential to lead to cross-resistance where drugs that are structurally related or share similar binding mechanisms all become less effective. PLpro inhibitors are currently under development and many emerging PLpro inhibitors are derived from GRL0617, a repurposed SARS-CoV PLpro inhibitor with moderate activity against SARS-CoV-2. Two...

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PMID: 40911642
DOI: 10.1371/journal.ppat.1013468
PMCID: PMC12431669

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