{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T08:07:07Z","timestamp":1753862827252,"version":"3.41.2"},"reference-count":56,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2023,11,15]],"date-time":"2023-11-15T00:00:00Z","timestamp":1700006400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["CHE-2102563"],"award-info":[{"award-number":["CHE-2102563"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chemistry &amp; Biodiversity"],"published-print":{"date-parts":[[2023,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>As COVID\u201019 infection caused severe public health concerns recently, the development of novel antivirals has become the need of the hour. Main protease (M<jats:sup>pro<\/jats:sup>) has been an attractive target for antiviral drugs since it plays a vital role in polyprotein processing and virus maturation. Herein we report the discovery of a novel class of inhibitors against the SARS\u2010CoV\u20102, bearing histidine <jats:italic>\u03b1<\/jats:italic>\u2010nitrile motif embedded on a simple dipeptide framework. <jats:italic>In\u2010vitro<\/jats:italic> and <jats:italic>in\u2010silico<\/jats:italic> studies revealed that the histidine <jats:italic>\u03b1<\/jats:italic>\u2010nitrile motif envisioned to target the M<jats:sup>pro<\/jats:sup> contributes to the inhibitory activity. Among a series of dipeptides synthesized featuring this novel structural motif, some dipeptides displayed strong viral reduction (EC<jats:sub>50<\/jats:sub>=0.48\u2005\u03bcM) with a high selectivity index, SI&gt;454.54. These compounds also exhibit strong binding energies in the range of \u221228.7 to \u221234.2\u2005Kcal\/mol. The simple dipeptide structural framework, amenable to quick structural variations, coupled with ease of synthesis from readily available commercial starting materials are the major attractive features of this novel class of SARS\u2010CoV\u20102 inhibitors. The histidine <jats:italic>\u03b1<\/jats:italic>\u2010nitrile dipeptides raise the hope of discovering potent drug candidates based on this motif to fight the dreaded SARS\u2010CoV\u20102.<\/jats:p>","DOI":"10.1002\/cbdv.202300957","type":"journal-article","created":{"date-parts":[[2023,10,27]],"date-time":"2023-10-27T12:34:06Z","timestamp":1698410046000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Discovery of SARS\u2010CoV\u20102 Inhibitors Featuring Novel Histidine <i>\u03b1<\/i>\u2010Nitrile Motif"],"prefix":"10.1002","volume":"20","author":[{"given":"Nilu","family":"Vijay Gone","sequence":"first","affiliation":[{"name":"Organic Chemistry Division CSIR-National Chemical Laboratory  Dr. Homi Bhabha Road Pune 411008 India"},{"name":"Academy of Scientific and Innovative Research (AcSIR)  Ghaziabad 201002 India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammed","family":"Ghalib Enayathullah","sequence":"additional","affiliation":[{"name":"Annexe-II, Medical Biotechnology Complex CSIR-Centre for Cellular and Molecular Biology  Uppal Road Hyderabad Telangana 500007 India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessie","family":"Thomas","sequence":"additional","affiliation":[{"name":"Annexe-II, Medical Biotechnology Complex CSIR-Centre for Cellular and Molecular Biology  Uppal Road Hyderabad Telangana 500007 India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Parth","family":"Rathee","sequence":"additional","affiliation":[{"name":"Department of Chemistry University of Miami  Coral Gables FL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rajeev","family":"Prabhakar","sequence":"additional","affiliation":[{"name":"Department of Chemistry University of Miami  Coral Gables FL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kiran","family":"Kumar Bokara","sequence":"additional","affiliation":[{"name":"Annexe-II, Medical Biotechnology Complex CSIR-Centre for Cellular and Molecular Biology  Uppal Road Hyderabad Telangana 500007 India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7764-7329","authenticated-orcid":false,"given":"Gangadhar J.","family":"Sanjayan","sequence":"additional","affiliation":[{"name":"Organic Chemistry Division CSIR-National Chemical Laboratory  Dr. Homi Bhabha Road Pune 411008 India"},{"name":"Academy of Scientific and Innovative Research (AcSIR)  Ghaziabad 201002 India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,11,15]]},"reference":[{"key":"e_1_2_9_1_1","unstructured":"\u201cWHO Coronavirus (COVID-19) Dashboard | WHO Coronavirus (COVID-19) Dashboard with Vaccination Data \u201d can be found underhttps:\/\/covid19.who.int\/."},{"key":"e_1_2_9_2_1","first-page":"1","volume":"16","author":"Anand N. 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