{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T11:19:19Z","timestamp":1778498359686,"version":"3.51.4"},"reference-count":55,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2022,9,7]],"date-time":"2022-09-07T00:00:00Z","timestamp":1662508800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002383","name":"King Saud University, Riyadh, Saudi Arabia","doi-asserted-by":"publisher","award":["RSP-2021\/64"],"award-info":[{"award-number":["RSP-2021\/64"]}],"id":[{"id":"10.13039\/501100002383","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Prince Sultan University","award":["RSP-2021\/64"],"award-info":[{"award-number":["RSP-2021\/64"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>During the past two decades, the world has witnessed the emergence of various SARS-CoV-2 variants with distinct mutational profiles influencing the global health, economy, and clinical aspects of the COVID-19 pandemic. These variants or mutants have raised major concerns regarding the protection provided by neutralizing monoclonal antibodies and vaccination, rates of virus transmission, and\/or the risk of reinfection. The newly emerged Omicron, a genetically distinct lineage of SARS-CoV-2, continues its spread in the face of rising vaccine-induced immunity while maintaining its replication fitness. Efforts have been made to improve the therapeutic interventions and the FDA has issued Emergency Use Authorization for a few monoclonal antibodies and drug treatments for COVID-19. However, the current situation of rapidly spreading Omicron and its lineages demands the need for effective therapeutic interventions to reduce the COVID-19 pandemic. Several experimental studies have indicated that the FDA-approved monoclonal antibodies are less effective than antiviral drugs against the Omicron variant. Thus, in this study, we aim to identify antiviral compounds against the Spike protein of Omicron, which binds to the human angiotensin-converting enzyme 2 (ACE2) receptor and facilitates virus invasion. Initially, docking-based virtual screening of the in-house database was performed to extract the potential hit compounds against the Spike protein. The obtained hits were optimized by DFT calculations to determine the electronic properties and molecular reactivity of the compounds. Further, MD simulation studies were carried out to evaluate the dynamics of protein\u2013ligand interactions at an atomistic level in a time-dependent manner. Collectively, five compounds (AKS-01, AKS-02, AKS-03, AKS-04, and AKS-05) with diverse scaffolds were identified as potential hits against the Spike protein of Omicron. Our study paves the way for further in vitro and in vivo studies.<\/jats:p>","DOI":"10.3390\/ijms231810315","type":"journal-article","created":{"date-parts":[[2022,9,7]],"date-time":"2022-09-07T20:52:03Z","timestamp":1662583923000},"page":"10315","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Cheminformatics-Based Discovery of Potential Chemical Probe Inhibitors of Omicron Spike Protein"],"prefix":"10.3390","volume":"23","author":[{"given":"Salman Ali","family":"Khan","sequence":"first","affiliation":[{"name":"Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alamgir","family":"Khan","sequence":"additional","affiliation":[{"name":"H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Komal","family":"Zia","sequence":"additional","affiliation":[{"name":"Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7988-7358","authenticated-orcid":false,"given":"Ihab","family":"Shawish","sequence":"additional","affiliation":[{"name":"Department of Math and Sciences, College of Humanities and Sciences, Prince Sultan University, P.O. Box 66833, Riyadh 11586, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7885-3201","authenticated-orcid":false,"given":"Assem","family":"Barakat","sequence":"additional","affiliation":[{"name":"Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8530-8711","authenticated-orcid":false,"given":"Zaheer","family":"Ul-Haq","sequence":"additional","affiliation":[{"name":"Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan"},{"name":"H.E.J. 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