{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T15:11:11Z","timestamp":1772118671976,"version":"3.50.1"},"reference-count":76,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2023,12,7]],"date-time":"2023-12-07T00:00:00Z","timestamp":1701907200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001843","name":"Science and Engineering Research Board","doi-asserted-by":"publisher","award":["IPA\/2020\/000054"],"award-info":[{"award-number":["IPA\/2020\/000054"]}],"id":[{"id":"10.13039\/501100001843","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["iubmb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["IUBMB Life"],"published-print":{"date-parts":[[2024,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The coronavirus disease 2019 (COVID\u201019) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS\u2010CoV\u20102) may be over, but its variants continue to emerge, and patients with mild symptoms having long COVID is still under investigation. SARS\u2010CoV\u20102 infection leading to elevated cytokine levels and suppressed immune responses set off cytokine storm, fatal systemic inflammation, tissue damage, and multi\u2010organ failure. Thus, drug molecules targeting the SARS\u2010CoV\u20102 virus\u2010specific proteins or capable of suppressing the host inflammatory responses to viral infection would provide an effective antiviral therapy against emerging variants of concern. Evolutionarily conserved papain\u2010like protease (PLpro) and main protease (Mpro) play an indispensable role in the virus life cycle and immune evasion. Direct\u2010acting antivirals targeting both these viral proteases represent an attractive antiviral strategy that is also expected to reduce viral inflammation. The present study has evaluated the antiviral and anti\u2010inflammatory potential of natural triterpenoids: azadirachtin, withanolide_A, and isoginkgetin. These molecules inhibit the Mpro and PLpro proteolytic activities with half\u2010maximal inhibitory concentrations (IC\n                    <jats:sub>50<\/jats:sub>\n                    ) values ranging from 1.42 to 32.7\u2009\u03bcM. Isothermal titration calorimetry (ITC) analysis validated the binding of these compounds to Mpro and PLpro. As expected, the two compounds, withanolide_A and azadirachtin, exhibit potent anti\u2010SARS\u2010CoV\u20102 activity in cell\u2010based assays, with half\u2010maximum effective concentration (EC\n                    <jats:sub>50<\/jats:sub>\n                    ) values of 21.73 and 31.19\u2009\u03bcM, respectively. The anti\u2010inflammatory roles of azadirachtin and withanolide_A when assessed using HEK293T cells, were found to significantly reduce the levels of CXCL10, TNF\u03b1, IL6, and IL8 cytokines, which are elevated in severe cases of COVID\u201019. Interestingly, azadirachtin and withanolide_A were also found to rescue the decreased type\u2010I interferon response (IFN\u2010\u03b11). The results of this study clearly highlight the role of triterpenoids as effective antiviral molecules that target SARS\u2010CoV\u20102\u2010specific enzymes and also host immune pathways involved in virus\u2010mediated inflammation.\n                  <\/jats:p>","DOI":"10.1002\/iub.2793","type":"journal-article","created":{"date-parts":[[2023,12,7]],"date-time":"2023-12-07T21:22:15Z","timestamp":1701984135000},"page":"228-241","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Unraveling antiviral efficacy of multifunctional immunomodulatory triterpenoids against\n                    <scp>SARS\u2010COV<\/scp>\n                    \u20102 targeting main protease and papain\u2010like protease"],"prefix":"10.1002","volume":"76","author":[{"given":"Shweta","family":"Choudhary","sequence":"first","affiliation":[{"name":"Department of Biosciences and Bioengineering Indian Institute of Technology Roorkee  Roorkee 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