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• W4295706178 abstract "The main protease (Mpro) of the SARS-CoV-2 virus is an attractive therapeutic target for developing antivirals to combat COVID-19. Mpro is essential for the replication cycle of the SARS-CoV-2 virus, so inhibiting Mpro blocks a vital piece of the cell replication machinery of the virus. A promising strategy to disrupt the viral replication cycle is to design inhibitors that bind to the active site cysteine (Cys145) of the Mpro. Cysteine targeted covalent inhibitors are gaining traction in drug discovery owing to the benefits of improved potency and extended drug-target engagement. An interesting aspect of these inhibitors is that they can be chemically tuned to form a covalent, but reversible bond, with their targets of interest. Several small-molecule cysteine-targeting covalent inhibitors of the Mpro have been discovered-some of which are currently undergoing evaluation in early phase human clinical trials. Understanding the binding energetics of these inhibitors could provide new insights to facilitate the design of potential drug candidates against COVID-19. Motivated by this, we employed rigorous absolute binding free energy calculations and hybrid quantum mechanical/molecular mechanical (QM/MM) calculations to estimate the energetics of binding of some promising reversible covalent inhibitors of the Mpro. We find that the inclusion of enhanced sampling techniques such as replica-exchange algorithm in binding free energy calculations can improve the convergence of predicted non-covalent binding free energy estimates of inhibitors binding to the Mpro target. In addition, our results indicate that binding free energy calculations coupled with multiscale simulations can be a useful approach to employ in ranking covalent inhibitors to their targets. This approach may be valuable in prioritizing and refining covalent inhibitor compounds for lead discovery efforts against COVID-19 and other coronavirus infections." @default.
• W4295706178 created "2022-09-14" @default.
• W4295706178 creator A5065514882 @default.
• W4295706178 date "2022-01-01" @default.
• W4295706178 modified "2023-09-26" @default.
• W4295706178 title "Estimating the binding energetics of reversible covalent inhibitors of the SARS-CoV-2 main protease: an <i>in silico</i> study" @default.
• W4295706178 cites W1031578623 @default.
• W4295706178 cites W1587176568 @default.
• W4295706178 cites W1883224873 @default.
• W4295706178 cites W1976499671 @default.
• W4295706178 cites W2010993054 @default.
• W4295706178 cites W2020735361 @default.
• W4295706178 cites W2021019774 @default.
• W4295706178 cites W2024762727 @default.
• W4295706178 cites W2027484375 @default.
• W4295706178 cites W2035687084 @default.
• W4295706178 cites W2037535298 @default.
• W4295706178 cites W2055110283 @default.
• W4295706178 cites W2055648985 @default.
• W4295706178 cites W2063206968 @default.
• W4295706178 cites W2067174909 @default.
• W4295706178 cites W2069924395 @default.
• W4295706178 cites W2072604508 @default.
• W4295706178 cites W2072683434 @default.
• W4295706178 cites W2078585784 @default.
• W4295706178 cites W2080974280 @default.
• W4295706178 cites W2081693079 @default.
• W4295706178 cites W2083116013 @default.
• W4295706178 cites W2103034037 @default.
• W4295706178 cites W2130479394 @default.
• W4295706178 cites W2140841928 @default.
• W4295706178 cites W2147993766 @default.
• W4295706178 cites W2153977062 @default.
• W4295706178 cites W2171291163 @default.
• W4295706178 cites W2327533467 @default.
• W4295706178 cites W248383993 @default.
• W4295706178 cites W2511380352 @default.
• W4295706178 cites W2511955955 @default.
• W4295706178 cites W2517550655 @default.
• W4295706178 cites W2527718275 @default.
• W4295706178 cites W2560915683 @default.
• W4295706178 cites W2598528124 @default.
• W4295706178 cites W2762419582 @default.
• W4295706178 cites W2884072597 @default.
• W4295706178 cites W2911268412 @default.
• W4295706178 cites W2998840182 @default.
• W4295706178 cites W3011701533 @default.
• W4295706178 cites W3015608194 @default.
• W4295706178 cites W3020300207 @default.
• W4295706178 cites W3021411957 @default.
• W4295706178 cites W3025838913 @default.
• W4295706178 cites W3033737840 @default.
• W4295706178 cites W3034228022 @default.
• W4295706178 cites W3034934060 @default.
• W4295706178 cites W3037323356 @default.
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• W4295706178 doi "https://doi.org/10.1039/d2cp03080b" @default.
• W4295706178 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/36128834" @default.
• W4295706178 hasPublicationYear "2022" @default.
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