{"doi":"10.1101/2022.01.26.477774","title":"The P132H mutation in the main protease of Omicron SARS-CoV-2 decreases thermal stability without compromising catalysis or small-molecule drug inhibition","abstract":"ABSTRACT The ongoing SARS-CoV-2 pandemic continues to be a significant threat to global health. First reported in November 2021, the Omicron variant (B.1.1.529) is more transmissible and can evade immunity better than previous SARS-CoV-2 variants, fueling an unprecedented surge in cases. To produce functional proteins from this polyprotein, SARS-CoV-2 relies on the cysteine proteases Nsp3/papain-like protease (PLpro) and Nsp5/Main Protease (M pro )/3C-like protease to cleave at three and more than 11 sites, respectively. 1 Therefore, M pro and PL pro inhibitors are considered to be some of the most promising SARS-CoV-2 antivirals. On December 22, 2021, the Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) for PAXLOVID, a ritonavir-boosted formulation of nirmatrelvir. Nirmatrelvir is a first-in-class orally bioavailable SARS-CoV-2 M pro inhibitor. 2 Thus, the scientific community must vigilantly monitor potential mechanisms of drug resistance, especially because SARS-CoV-2 is naïve to M pro inhibitors. Mutations have been well identified in variants to this point. 3 Notably, Omicron M pro (OM pro ) harbors a single mutation– P132H. In this study we characterize the enzymatic activity, drug inhibition, and structure of OM pro while evaluating the past and future implications of M pro mutations.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":297329,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":10,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9465,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":107690,"name":"Yanmei Hu","orcid":"0000-0003-0525-7342","position":1,"is_corresponding":false},{"id":845592,"name":"Maura V. Gongora","orcid":"0000-0002-7151-950X","position":2,"is_corresponding":false},{"id":845593,"name":"Flora Meilleur","orcid":"0000-0001-9313-8989","position":3,"is_corresponding":false},{"id":846854,"name":"M. Trent Kemp","orcid":null,"position":4,"is_corresponding":false},{"id":107692,"name":"Xiujun Zhang","orcid":"0000-0001-8041-0592","position":5,"is_corresponding":false},{"id":107696,"name":"Jun Wang","orcid":"0000-0002-4845-4621","position":6,"is_corresponding":false},{"id":107695,"name":"Yu Chen","orcid":"0000-0002-5115-3600","position":7,"is_corresponding":false},{"id":107687,"name":"M. Sacco","orcid":"0000-0001-5930-7363","position":0,"is_corresponding":true}],"reference_count":9,"raw_metadata":null,"created_at":"2026-07-19T00:31:26.161109Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}