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The emerging variants Omicron and its sublineage have a greater ability to spread and escape nearly all current monoclonal antibodies treatments, highlighting an urgent need to develop therapeutics targeting current and emerging Omicron variants or recombinants with breadth and potency. Here, some small molecule drugs are rapidly identified that could covalently binding to receptor binding domain (RBD) protein of Omicron through the combined application of artificial intelligence (AI) and activity\u2010based protein profiling (ABPP) technology. The surface plasmon resonance (SPR) and pseudo\u2010virus neutralization experiments further reveal that an FDA\u2010approved drug gallic acid has robust neutralization potency against Omicron pseudo\u2010virus with the IC<jats:sub>50<\/jats:sub> values of 23.56 \u00d7 10<jats:sup>\u22126<\/jats:sup> <jats:sc>m<\/jats:sc>. Taken together, a platform combining AI intelligence, biochemical, SPR, molecular docking, and pseudo\u2010virus\u2010based screening for rapid identification and evaluation of potential anti\u2010SARS\u2010CoV\u20102 small molecule drugs is established and the effectiveness of the platform is validated.<\/jats:p>","DOI":"10.1002\/adbi.202300612","type":"journal-article","created":{"date-parts":[[2024,10,16]],"date-time":"2024-10-16T02:49:35Z","timestamp":1729046975000},"source":"Crossref","is-referenced-by-count":1,"title":["Chemical Proteomics Approaches for Screening Small Molecule Inhibitors Covalently Binding to SARS\u2010Cov\u20102"],"prefix":"10.1002","volume":"8","author":[{"given":"Liuhai","family":"Zheng","sequence":"first","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine Guangdong Provincial Clinical Research Center for Geriatrics, Shenzhen Institute of Respiratory Diseases and Shenzhen Clinical Research Centre for Geriatrics Shenzhen People's 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