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000482648 1001_ $$0P:(DE-H253)PIP1080622$$aSrinivasan, Vasundara$$b0$$eCorresponding author
000482648 245__ $$aAntiviral activity of natural phenolic compounds in complex at an allosteric site of SARS-CoV-2 papain-like protease
000482648 260__ $$aLondon$$bSpringer Nature$$c2022
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000482648 520__ $$aSARS-CoV-2 papain-like protease (PLpro) covers multiple functions. Beside the cysteine-protease activity, facilitating cleavage of the viral polypeptide chain, PLpro has the additional and vital function of removing ubiquitin and ISG15 (Interferon-stimulated gene 15) from host-cell proteins to support coronaviruses in evading the host’s innate immune responses. We identified three phenolic compounds bound to PLpro, preventing essential molecular interactions to ISG15 by screening a natural compound library. The compounds identified by X-ray screening and complexed to PLpro demonstrate clear inhibition of PLpro in a deISGylation activity assay. Two compounds exhibit distinct antiviral activity in Vero cell line assays and one inhibited a cytopathic effect in non-cytotoxic concentration ranges. In the context of increasing PLpro mutations in the evolving new variants of SARS-CoV-2, the natural compounds we identified may also reinstate the antiviral immune response processes of the host that are down-regulated in COVID-19 infections.
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000482648 773__ $$0PERI:(DE-600)2919698-X$$a10.1038/s42003-022-03737-7$$gVol. 5, no. 1, p. 805$$n1$$p805$$tCommunications biology$$v5$$x2399-3642$$y2022
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