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- W4328127360 abstract "The main protease of SARS-CoV-2 (Mpro) is the most promising drug target against coronaviruses due to its essential role in virus replication. With newly emerging variants there is a concern that mutations in Mpro may alter the structural and functional properties of protease and subsequently the potency of existing and potential antivirals. We explored the effect of 31 mutations belonging to 5 variants of concern (VOCs) on catalytic parameters and substrate specificity, which revealed changes in substrate binding and the rate of cleavage of a viral peptide. Crystal structures of 11 Mpro mutants provided structural insight into their altered functionality. Additionally, we show Mpro mutations influence proteolysis of an immunomodulatory host protein Galectin-8 (Gal-8) and a subsequent significant decrease in cytokine secretion, providing evidence for alterations in the escape of host-antiviral mechanisms. Accordingly, mutations associated with the Gamma VOC and highly virulent Delta VOC resulted in a significant increase in Gal-8 cleavage. Importantly, IC50s of nirmatrelvir (Pfizer) and our irreversible inhibitor AVI-8053 demonstrated no changes in potency for both drugs for all mutants, suggesting Mpro will remain a high-priority antiviral drug candidate as SARS-CoV-2 evolves." @default.
- W4328127360 created "2023-03-22" @default.
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- W4328127360 date "2023-03-21" @default.
- W4328127360 modified "2023-10-10" @default.
- W4328127360 title "SARS-CoV-2 M<sup>pro</sup> Protease Variants of Concern Display Altered Viral Substrate and Cell Host Target Galectin-8 Processing but Retain Sensitivity toward Antivirals" @default.
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- W4328127360 cites W2083371701 @default.
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- W4328127360 cites W2140915719 @default.
- W4328127360 cites W2141361007 @default.
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- W4328127360 cites W3165952552 @default.
- W4328127360 cites W3167205542 @default.
- W4328127360 cites W3178949565 @default.
- W4328127360 cites W3179206042 @default.
- W4328127360 cites W3179854196 @default.
- W4328127360 cites W3189646261 @default.
- W4328127360 cites W3193440777 @default.
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- W4328127360 doi "https://doi.org/10.1021/acscentsci.3c00054" @default.
- W4328127360 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/37122453" @default.
- W4328127360 hasPublicationYear "2023" @default.
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