{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T14:27:14Z","timestamp":1789050434715,"version":"build-2803163510"},"reference-count":49,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100007488","name":"Indian Institute of Technology Delhi","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007488","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014825","name":"Biotechnology Industry Research Assistance Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100014825","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001407","name":"Government of India Department of Biotechnology","doi-asserted-by":"publisher","award":["BT\/COVID0016\/01\/20"],"award-info":[{"award-number":["BT\/COVID0016\/01\/20"]}],"id":[{"id":"10.13039\/501100001407","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["European Journal of Medicinal Chemistry"],"published-print":{"date-parts":[[2026,9]]},"DOI":"10.1016\/j.ejmech.2026.118919","type":"journal-article","created":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T15:09:58Z","timestamp":1777561798000},"page":"118919","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":1,"special_numbering":"C","title":["Novobiocin defines an Asn28 allosteric pocket that governs SARS-CoV-2 main protease activity"],"prefix":"10.1016","volume":"314","author":[{"given":"Mohit","family":"Bhardwaj","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raushan","family":"Anjum","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheetal","family":"Thakur","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pradeep","family":"Sharma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6134-7794","authenticated-orcid":false,"given":"Ashok Kumar","family":"Patel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"4","key":"10.1016\/j.ejmech.2026.118919_bib1","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1038\/s41579-021-00639-z","article-title":"Infectious disease in an era of global change","volume":"20","author":"Baker","year":"2021","journal-title":"Nat. Rev. Microbiol."},{"issue":"3","key":"10.1016\/j.ejmech.2026.118919_bib2","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1038\/s41579-020-00459-7","article-title":"Characteristics of SARS-CoV-2 and COVID-19","volume":"19","author":"Hu","year":"2020","journal-title":"Nat. Rev. Microbiol."},{"issue":"8","key":"10.1016\/j.ejmech.2026.118919_bib3","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1016\/j.jiph.2021.06.007","article-title":"Meta-analysis and comprehensive study of coronavirus outbreaks: SARS, MERS and COVID-19","volume":"14","author":"Berber","year":"2021","journal-title":"J. Infect. Public Health"},{"issue":"8","key":"10.1016\/j.ejmech.2026.118919_bib4","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.3390\/jpm12081295","article-title":"Global challenges to public health care systems during the COVID-19 pandemic: a review of pandemic measures and problems","volume":"12","author":"Filip","year":"2022","journal-title":"J. Personalized Med."},{"issue":"4","key":"10.1016\/j.ejmech.2026.118919_bib5","doi-asserted-by":"crossref","first-page":"424","DOI":"10.3390\/vaccines13040424","article-title":"Beyond the pandemic era: recent advances and efficacy of SARS-CoV-2 vaccines against emerging variants of concern","volume":"13","author":"Saha","year":"2025","journal-title":"Vaccines"},{"issue":"10","key":"10.1016\/j.ejmech.2026.118919_bib6","doi-asserted-by":"crossref","first-page":"1646","DOI":"10.3390\/ani13101646","article-title":"The impact of human activities on zoonotic infection transmissions","volume":"13","author":"Esposito","year":"2023","journal-title":"Animals"},{"issue":"1 Suppl 1","key":"10.1016\/j.ejmech.2026.118919_bib7","doi-asserted-by":"crossref","DOI":"10.1590\/1678-4685-gmb-2020-0355","article-title":"Zoonotic spillover: understanding basic aspects for better prevention","volume":"44","author":"Ellwanger","year":"2021","journal-title":"Genet. Mol. Biol."},{"issue":"6","key":"10.1016\/j.ejmech.2026.118919_bib8","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1016\/j.cmi.2020.03.026","article-title":"COVID-19, SARS and MERS: are they closely related?","volume":"26","author":"Petrosillo","year":"2020","journal-title":"Clin. Microbiol. Infection"},{"key":"10.1016\/j.ejmech.2026.118919_bib9","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.pedn.2020.10.020","article-title":"Human coronaviruses SARS-CoV, MERS-CoV, and SARS-CoV-2 in children","volume":"56","author":"Aleebrahim-Dehkordi","year":"2020","journal-title":"J. Pediatr. Nurs."},{"issue":"1","key":"10.1016\/j.ejmech.2026.118919_bib10","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1038\/s41580-021-00418-x","article-title":"Mechanisms of SARS-CoV-2 entry into cells","volume":"23","author":"Jackson","year":"2021","journal-title":"Nat. Rev. Mol. Cell Biol."},{"issue":"3","key":"10.1016\/j.ejmech.2026.118919_bib11","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1038\/s41579-020-00468-6","article-title":"Coronavirus biology and replication: implications for SARS-CoV-2","volume":"19","author":"V\u2019kovski","year":"2020","journal-title":"Nat. Rev. Microbiol."},{"issue":"21","key":"10.1016\/j.ejmech.2026.118919_bib12","doi-asserted-by":"crossref","first-page":"11727","DOI":"10.1073\/pnas.2003138117","article-title":"Cell entry mechanisms of SARS-CoV-2","volume":"117","author":"Shang","year":"2020","journal-title":"Proc. Natl. Acad. Sci. U. S. A"},{"issue":"5","key":"10.1016\/j.ejmech.2026.118919_bib13","doi-asserted-by":"crossref","DOI":"10.1016\/j.jbc.2023.104697","article-title":"SARS-CoV-2 polyprotein substrate regulates the stepwise mpro cleavage reaction","volume":"299","author":"Narwal","year":"2023","journal-title":"J. Biol. Chem."},{"issue":"5626","key":"10.1016\/j.ejmech.2026.118919_bib14","doi-asserted-by":"crossref","first-page":"1763","DOI":"10.1126\/science.1085658","article-title":"Coronavirus main proteinase (3CLpro) structure: basis for design of anti-SARS drugs","volume":"300","author":"Anand","year":"2003","journal-title":"Science"},{"issue":"6","key":"10.1016\/j.ejmech.2026.118919_bib15","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1021\/acscombsci.0c00058","article-title":"Targeting the dimerization of the main protease of coronaviruses: a potential broad-spectrum therapeutic strategy","volume":"22","author":"Goyal","year":"2020","journal-title":"ACS Comb. Sci."},{"issue":"50","key":"10.1016\/j.ejmech.2026.118919_bib16","doi-asserted-by":"crossref","first-page":"14908","DOI":"10.1021\/bi0616302","article-title":"Long-Range cooperative interactions modulate dimerization in SARS 3CLpro","volume":"45","author":"Barrila","year":"2006","journal-title":"Biochemistry"},{"issue":"3","key":"10.1016\/j.ejmech.2026.118919_bib17","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1016\/j.bbrc.2005.11.102","article-title":"The N-terminal octapeptide acts as a dimerization inhibitor of SARS coronavirus 3C-like proteinase","volume":"339","author":"Wei","year":"2006","journal-title":"Biochem. Biophys. Res. Commun."},{"issue":"7811","key":"10.1016\/j.ejmech.2026.118919_bib18","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1038\/s41586-020-2223-y","article-title":"Structure of Mpro from SARS-CoV-2 and discovery of its inhibitors","volume":"582","author":"Jin","year":"2020","journal-title":"Nature"},{"issue":"1","key":"10.1016\/j.ejmech.2026.118919_bib19","doi-asserted-by":"crossref","first-page":"5877","DOI":"10.1038\/s41467-020-19662-4","article-title":"Crystallographic structure of wild-type SARS-CoV-2 main protease acyl-enzyme intermediate with physiological C-terminal autoprocessing site","volume":"11","author":"Lee","year":"2020","journal-title":"Nat. Commun."},{"issue":"6","key":"10.1016\/j.ejmech.2026.118919_bib20","doi-asserted-by":"crossref","first-page":"452","DOI":"10.4103\/ijp.ijp_291_22","article-title":"Paxlovid: a promising drug for the challenging treatment of SARS-COV-2 in the pandemic era","volume":"54","author":"Niraj","year":"2023","journal-title":"Indian J. Pharmacol."},{"issue":"1","key":"10.1016\/j.ejmech.2026.118919_bib21","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1038\/s42003-023-05071-y","article-title":"Molecular mechanism of ensitrelvir inhibiting SARS-CoV-2 main protease and its variants","volume":"6","author":"Lin","year":"2023","journal-title":"Commun. Biol."},{"issue":"1","key":"10.1016\/j.ejmech.2026.118919_bib22","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1038\/s43856-025-00863-1","article-title":"Targeted protein degraders of SARS-CoV-2 Mpro are more active than enzymatic inhibition alone with activity against nirmatrelvir resistant virus","volume":"5","author":"Pan","year":"2025","journal-title":"Commun. Med."},{"key":"10.1016\/j.ejmech.2026.118919_bib23","doi-asserted-by":"crossref","DOI":"10.1016\/j.ijbiomac.2025.142765","article-title":"Allosteric mutations impact the catalytic activity and oligomeric state of the main protease of coronavirus","volume":"309","author":"Bhardwaj","year":"2025","journal-title":"Int. J. Biol. Macromol."},{"issue":"18","key":"10.1016\/j.ejmech.2026.118919_bib24","doi-asserted-by":"crossref","first-page":"9920","DOI":"10.1093\/nar\/gkad727","article-title":"Novobiocin blocks nucleic acid binding to Pol\u03b8 and inhibits stimulation of its ATPase activity","volume":"51","author":"Syed","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.ejmech.2026.118919_bib25","series-title":"Kucers' the Use of Antibiotics","author":"Mouton","year":"2017"},{"issue":"2","key":"10.1016\/j.ejmech.2026.118919_bib26","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1021\/acscentsci.2c01359","article-title":"Development of highly potent noncovalent inhibitors of SARS-CoV-2 3CLpro","volume":"9","author":"Hou","year":"2023","journal-title":"ACS Cent. Sci."},{"issue":"3","key":"10.1016\/j.ejmech.2026.118919_bib27","article-title":"Paxlovid (Nirmatrelvir\/Ritonavir): a new approach to Covid-19 therapy?","volume":"162","author":"Hashemian","year":"2023","journal-title":"Biomed. Pharmacother."},{"issue":"1","key":"10.1016\/j.ejmech.2026.118919_bib28","article-title":"Oral 3CL protease inhibitor ensitrelvir suppressed SARS-CoV-2 shedding and infection in a hamster aerosol transmission model","volume":"232","author":"Nakashima","year":"2024","journal-title":"Antivir. Res."},{"key":"10.1016\/j.ejmech.2026.118919_bib29","doi-asserted-by":"crossref","DOI":"10.3389\/fmolb.2020.601065","article-title":"RASPD+: fast protein-ligand binding free energy prediction using simplified physicochemical features","volume":"7","author":"Holderbach","year":"2020","journal-title":"Front. Mol. Biosci."},{"issue":"7","key":"10.1016\/j.ejmech.2026.118919_bib30","doi-asserted-by":"crossref","first-page":"632","DOI":"10.2174\/092986607781483831","article-title":"ParDOCK: an all atom energy based monte carlo docking protocol for protein-ligand complexes","volume":"14","author":"A","year":"2007","journal-title":"Protein Pept. Lett."},{"key":"10.1016\/j.ejmech.2026.118919_bib31","author":"Case Ross C Walker"},{"issue":"8","key":"10.1016\/j.ejmech.2026.118919_bib32","doi-asserted-by":"crossref","first-page":"3696","DOI":"10.1021\/acs.jctc.5b00255","article-title":"ff14SB: improving the accuracy of protein side chain and backbone parameters from ff99SB","volume":"11","author":"Maier","year":"2015","journal-title":"J. Chem. Theor. Comput."},{"issue":"2","key":"10.1016\/j.ejmech.2026.118919_bib33","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1063\/1.445869","article-title":"Comparison of simple potential functions for simulating liquid water","volume":"79","author":"Jorgensen","year":"1983","journal-title":"J. Chem. Phys."},{"issue":"9","key":"10.1016\/j.ejmech.2026.118919_bib34","doi-asserted-by":"crossref","first-page":"3668","DOI":"10.1063\/1.470043","article-title":"Accuracy and efficiency of the particle mesh ewald method","volume":"103","author":"Petersen","year":"1995","journal-title":"J. Chem. Phys."},{"key":"10.1016\/j.ejmech.2026.118919_bib35","series-title":"The Molecular Dynamics of Liquid Crystals","first-page":"85","article-title":"Techniques and applications of langevin dynamics simulations","author":"Pastor","year":"1994"},{"issue":"8","key":"10.1016\/j.ejmech.2026.118919_bib36","doi-asserted-by":"crossref","first-page":"1689","DOI":"10.1021\/acs.jpca.8b09082","article-title":"New method for Constant- NPT molecular dynamics","volume":"123","author":"Kim","year":"2019","journal-title":"J. Phys. Chem. A"},{"issue":"10","key":"10.1016\/j.ejmech.2026.118919_bib37","doi-asserted-by":"crossref","first-page":"2043","DOI":"10.1021\/acs.jcim.8b00462","article-title":"GPU-accelerated molecular dynamics and free energy methods in Amber 18: performance enhancements and new features","volume":"58","author":"Lee","year":"2018","journal-title":"J. Chem. Inf. Model."},{"issue":"10","key":"10.1016\/j.ejmech.2026.118919_bib38","doi-asserted-by":"crossref","first-page":"2778","DOI":"10.1021\/ci200227u","article-title":"LigPlot+: multiple ligand-protein interaction diagrams for drug discovery","volume":"51","author":"Laskowski","year":"2011","journal-title":"J. Chem. Inf. Model."},{"issue":"11","key":"10.1016\/j.ejmech.2026.118919_bib40","doi-asserted-by":"crossref","DOI":"10.1002\/pro.4792","article-title":"scp>UCSF ChimeraX<\/scp> : tools for structure building and analysis","volume":"32","author":"Meng","year":"2023","journal-title":"Protein Sci."},{"issue":"20","key":"10.1016\/j.ejmech.2026.118919_bib41","doi-asserted-by":"crossref","first-page":"12562","DOI":"10.1073\/pnas.202427399","article-title":"Escaping free-energy minima","volume":"99","author":"Laio","year":"2002","journal-title":"Proc. Natl. Acad. Sci. U. S. A"},{"issue":"2","key":"10.1016\/j.ejmech.2026.118919_bib42","doi-asserted-by":"crossref","DOI":"10.1103\/PhysRevLett.100.020603","article-title":"Well-tempered metadynamics: a smoothly converging and tunable free-energy method","volume":"100","author":"Barducci","year":"2008","journal-title":"Phys. Rev. Lett."},{"issue":"2","key":"10.1016\/j.ejmech.2026.118919_bib43","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1016\/j.cpc.2013.09.018","article-title":"Plumed 2: new feathers for an old bird","volume":"185","author":"Tribello","year":"2014","journal-title":"Comput. Phys. Commun."},{"issue":"3","key":"10.1016\/j.ejmech.2026.118919_bib44","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1021\/jp504920s","article-title":"A time-independent free energy estimator for metadynamics","volume":"119","author":"Tiwary","year":"2014","journal-title":"J. Phys. Chem. B"},{"issue":"19","key":"10.1016\/j.ejmech.2026.118919_bib45","doi-asserted-by":"crossref","first-page":"6825","DOI":"10.1073\/pnas.0409005102","article-title":"Calculation of absolute protein-ligand binding free energy from computer simulations","volume":"102","author":"Woo","year":"2005","journal-title":"Proc. Natl. Acad. Sci. U. S. A"},{"issue":"7","key":"10.1016\/j.ejmech.2026.118919_bib46","doi-asserted-by":"crossref","first-page":"1463","DOI":"10.1021\/acs.biochem.5c00009","article-title":"Impact of cancer-associated PKM2 mutations on enzyme activity and allosteric regulation: structural and functional insights into metabolic reprogramming","volume":"64","author":"Upadhyay","year":"2025","journal-title":"Biochemistry"},{"issue":"Sep","key":"10.1016\/j.ejmech.2026.118919_bib47","article-title":"Sigma's non-specific protease activity assay - casein as a substrate","volume":"19","author":"Cupp-Enyard","year":"2008","journal-title":"J. Vis. Exp."},{"issue":"12","key":"10.1016\/j.ejmech.2026.118919_bib48","doi-asserted-by":"crossref","first-page":"3411","DOI":"10.1002\/ptr.6802","article-title":"Evaluation of medicinal herbs as a potential therapeutic option against SARS-CoV-2 targeting its main protease","volume":"34","author":"Upadhyay","year":"2020","journal-title":"Phytother Res."},{"issue":"6494","key":"10.1016\/j.ejmech.2026.118919_bib49","doi-asserted-by":"crossref","first-page":"2622","DOI":"10.1016\/j.ijbiomac.2020.08.166","article-title":"Screening and evaluation of approved drugs as inhibitors of main protease of SARS-CoV-2","volume":"164","author":"Tripathi","year":"2020","journal-title":"Int. J. Biol. Macromol."},{"issue":"1","key":"10.1016\/j.ejmech.2026.118919_bib50","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1002\/0471140864.ps2809s79","article-title":"Analysis of protein stability and ligand interactions by thermal shift assay","volume":"79","author":"Huynh","year":"2015","journal-title":"Curr. Protoc. Protein Sci."}],"container-title":["European Journal of Medicinal Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0223523426003648?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0223523426003648?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T22:04:30Z","timestamp":1783116270000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0223523426003648"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9]]},"references-count":49,"alternative-id":["S0223523426003648"],"URL":"https:\/\/doi.org\/10.1016\/j.ejmech.2026.118919","relation":{},"ISSN":["0223-5234"],"issn-type":[{"value":"0223-5234","type":"print"}],"subject":[],"published":{"date-parts":[[2026,9]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Novobiocin defines an Asn28 allosteric pocket that governs SARS-CoV-2 main protease activity","name":"articletitle","label":"Article Title"},{"value":"European Journal of Medicinal Chemistry","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ejmech.2026.118919","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 Elsevier Masson SAS. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"118919"}}