{"doi":"10.1002/jmv.26497","title":"The emerging SARS‐CoV‐2 papain‐like protease: Its relationship with recent coronavirus epidemics","abstract":"<jats:title>Abstract</jats:title><jats:sec><jats:label/><jats:p>The papain‐like protease (PL<jats:sup>pro</jats:sup>) is an important enzyme for coronavirus polyprotein processing, as well as for virus‐host immune suppression. Previous studies reveal that a molecular analysis of PL<jats:sup>pro</jats:sup> indicates the catalytic activity of viral PL<jats:sup>pro</jats:sup> and its interactions with ubiquitin. By using sequence comparisons, molecular models, and protein–protein interaction maps, PL<jats:sup>pro</jats:sup> was compared in the three recorded fatal CoV epidemics, which involved severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), severe acute respiratory syndrome CoV (SARS‐CoV), and Middle East respiratory syndrome coronavirus (MERS‐CoV). The pairwise sequence comparison of SARS‐CoV‐2 PL<jats:sup>pro</jats:sup> indicated similarity percentages of 82.59% and 30.06% with SARS‐CoV PL<jats:sup>pro</jats:sup> and MERS‐CoV PL<jats:sup>pro</jats:sup>, respectively. In comparison with SARS‐CoV PL<jats:sup>pro</jats:sup>, in SARS‐CoV‐2, the PL<jats:sup>pro</jats:sup> had a conserved catalytic triad of C111, H278, and D293, with a slightly lower number of polar interface residues and of hydrogen bonds, a higher number of buried interface sizes, and a lower number of residues that interact with ubiquitin and PL<jats:sup>pro</jats:sup>. These features might contribute to a similar or slightly lower level of deubiquitinating activity in SARS‐CoV‐2 PLpro. It was, however, a much higher level compared to MERS‐CoV, which contained amino acid mutations and a low number of polar interfaces. SARS‐CoV‐2 PL<jats:sup>pro</jats:sup> and SARS‐CoV PL<jats:sup>pro</jats:sup> showed almost the same catalytic site profiles, interface area compositions and polarities, suggesting a general similarity in deubiquitination activity. Compared with MERS‐CoV, SARS‐CoV‐2 had a higher potential for binding interactions with ubiquitin. These estimated parameters contribute to the knowledge gap in understanding how the new virus interacts with the immune system.</jats:p></jats:sec>","journal":"Journal of Medical Virology","year":2021,"id":604028,"datarank":0.41588830833596724,"base_score":2.772588722239781,"endowment":2.772588722239781,"self_citation_contribution":0.41588830833596724,"citation_network_contribution":0.0,"self_endowment_contribution":0.41588830833596724,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":15,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1549654,"name":"Yukio Kitade","orcid":null,"position":1,"is_corresponding":false},{"id":1549655,"name":"Mahmoud Fayez","orcid":"0000-0002-2145-2714","position":2,"is_corresponding":false},{"id":1549656,"name":"Katharigatta N. Venugopala","orcid":null,"position":3,"is_corresponding":false},{"id":1549657,"name":"Abdelazim Ibrahim","orcid":null,"position":4,"is_corresponding":false},{"id":1549652,"name":"Mahmoud Kandeel","orcid":"0000-0003-3668-5147","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"The emerging SARS‐CoV‐2 papain‐like protease: Its relationship with recent coronavirus epidemics","abstract":"<jats:title>Abstract</jats:title><jats:sec><jats:label/><jats:p>The papain‐like protease (PL<jats:sup>pro</jats:sup>) is an important enzyme for coronavirus polyprotein processing, as well as for virus‐host immune suppression. Previous studies reveal that a molecular analysis of PL<jats:sup>pro</jats:sup> indicates the catalytic activity of viral PL<jats:sup>pro</jats:sup> and its interactions with ubiquitin. By using sequence comparisons, molecular models, and protein–protein interaction maps, PL<jats:sup>pro</jats:sup> was compared in the three recorded fatal CoV epidemics, which involved severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), severe acute respiratory syndrome CoV (SARS‐CoV), and Middle East respiratory syndrome coronavirus (MERS‐CoV). The pairwise sequence comparison of SARS‐CoV‐2 PL<jats:sup>pro</jats:sup> indicated similarity percentages of 82.59% and 30.06% with SARS‐CoV PL<jats:sup>pro</jats:sup> and MERS‐CoV PL<jats:sup>pro</jats:sup>, respectively. In comparison with SARS‐CoV PL<jats:sup>pro</jats:sup>, in SARS‐CoV‐2, the PL<jats:sup>pro</jats:sup> had a conserved catalytic triad of C111, H278, and D293, with a slightly lower number of polar interface residues and of hydrogen bonds, a higher number of buried interface sizes, and a lower number of residues that interact with ubiquitin and PL<jats:sup>pro</jats:sup>. These features might contribute to a similar or slightly lower level of deubiquitinating activity in SARS‐CoV‐2 PLpro. It was, however, a much higher level compared to MERS‐CoV, which contained amino acid mutations and a low number of polar interfaces. SARS‐CoV‐2 PL<jats:sup>pro</jats:sup> and SARS‐CoV PL<jats:sup>pro</jats:sup> showed almost the same catalytic site profiles, interface area compositions and polarities, suggesting a general similarity in deubiquitination activity. Compared with MERS‐CoV, SARS‐CoV‐2 had a higher potential for binding interactions with ubiquitin. These estimated parameters contribute to the knowledge gap in understanding how the new virus interacts with the immune system.</jats:p></jats:sec>","is_dataset_classified":null,"base_score":0.0,"endowment":0.0,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"32902889","pmcid":null,"openalex_id":null,"authors":[],"funders":[{"funder_name":"Deanship of Scientific Research, King Faisal University","grant_id":"1811016","title":null}],"total_grants":1,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[],"oa_status":"closed","license":"http://onlinelibrary.wiley.com/termsAndConditions#vor","oa_locations":[{"url":"https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fjmv.26497","host_type":"publisher"},{"url":"https://onlinelibrary.wiley.com/doi/pdf/10.1002/jmv.26497","host_type":"publisher"},{"url":"https://onlinelibrary.wiley.com/doi/full-xml/10.1002/jmv.26497","host_type":"publisher"}],"fields_of_study":[],"mesh_terms":["Humans","Severe Acute Respiratory Syndrome","Polyproteins","Ubiquitin","Viral Proteins","Sequence Alignment","Amino Acid Sequence","Catalytic Domain","Models, Molecular","Middle East Respiratory Syndrome Coronavirus","COVID-19","SARS-CoV-2","Coronavirus Papain-Like Proteases","Severe acute respiratory syndrome-related coronavirus"],"keywords":["Molecular modeling","innate immunity","Papain-like Protease","Covid-19","Sars-cov-2"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-29T23:14:50.112149Z","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":[]}