{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T18:08:37Z","timestamp":1787162917863,"version":"build-2736575974"},"reference-count":57,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2023,2,18]],"date-time":"2023-02-18T00:00:00Z","timestamp":1676678400000},"content-version":"vor","delay-in-days":17,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Medical Virology"],"published-print":{"date-parts":[[2023,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The ongoing pandemic with the emergence of immune evasion potential and, particularly, the current omicron subvariants intensified the situation further. Although vaccines are available, the immune evasion capabilities of the recent variants demand further efficient therapeutic choices to control the severe acute respiratory syndrome coronavirus 2 (SARS\u2010CoV\u20102) pandemic. Hence, considering the necessity of the small molecule inhibitor, we target the main protease (3CLpro), which is an appealing target for the development of antiviral drugs against SARS\u2010CoV\u20102. High\u2010throughput molecular in silico screening of South African natural compounds database reported Isojacareubin and Glabranin as the potential inhibitors for the main protease. The calculated docking scores were reported to be \u22128.47 and \u22128.03\u2009kcal\/mol, respectively. Moreover, the structural dynamic assessment reported that Isojacareubin in complex with 3CLpro exhibit a more stable dynamic behavior than Glabranin. Inhibition assay indicated that Isojacareubin could inhibit SARS\u2010CoV\u20102 3CLpro in a time\u2010 and dose\u2010dependent manner, with half maximal inhibitory concentration values of 16.00\u2009\u00b1\u20091.35\u2009\u03bcM (60\u2009min incubation). Next, the covalent binding sites of Isojacareubin on SARS\u2010CoV\u20102 3CL\n                    <jats:sup>pro<\/jats:sup>\n                    was identified by biomass spectrometry, which reported that Isojacareubin can covalently bind to thiols or Cysteine through Michael addition. To evaluate the inactivation potency of Isojacareubin, the inactivation kinetics was further investigated. The inactivation kinetic curves were plotted according to various concentrations with gradient\u2010ascending incubation times. The\n                    <jats:italic>K<\/jats:italic>\n                    <jats:sub>I<\/jats:sub>\n                    value of Isojacareubin was determined as 30.71\u2009\u03bcM, whereas the\n                    <jats:italic>K<\/jats:italic>\n                    <jats:sub>inact<\/jats:sub>\n                    value was calculated as 0.054\u2009min\n                    <jats:sup>\u22121<\/jats:sup>\n                    . These results suggest that Isojacareubin is a covalent inhibitor of SARS\u2010CoV\u20102 3CL\n                    <jats:sup>pro<\/jats:sup>\n                    .\n                  <\/jats:p>","DOI":"10.1002\/jmv.28542","type":"journal-article","created":{"date-parts":[[2023,2,2]],"date-time":"2023-02-02T06:48:20Z","timestamp":1675320500000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Discovery of Isojacareubin as a covalent inhibitor of SARS\u2010CoV\u20102 main protease using structural and experimental approaches"],"prefix":"10.1002","volume":"95","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4288-7602","authenticated-orcid":false,"given":"Abbas","family":"Khan","sequence":"first","affiliation":[{"name":"Department of Bioinformatics and Biological Statistics, School of Life Sciences and Biotechnology Shanghai Jiao Tong University  Shanghai P.R. 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