{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T19:24:31Z","timestamp":1786994671112,"version":"build-2736575974"},"reference-count":42,"publisher":"American Chemical Society (ACS)","issue":"11","license":[{"start":{"date-parts":[[2020,8,6]],"date-time":"2020-08-06T00:00:00Z","timestamp":1596672000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2020,8,6]],"date-time":"2020-08-06T00:00:00Z","timestamp":1596672000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2020,8,6]],"date-time":"2020-08-06T00:00:00Z","timestamp":1596672000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,11,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Originating in the city of Wuhan in China in December 2019, COVID-19 has emerged now as a global health emergency with a high number of deaths worldwide. COVID-19 is caused by a novel coronavirus, referred to as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), resulting in pandemic conditions around the globe. We are in the battleground to fight against the virus by rapidly developing therapeutic strategies in tackling SARS-CoV-2 and saving human lives from COVID-19. Scientists are evaluating several known drugs either for the pathogen or the host; however, many of them are reported to be associated with side effects. In the present study, we report the molecular binding mechanisms of the natural alkaloid, noscapine, for repurposing against the main protease of SARS-CoV-2, a key enzyme involved in its reproduction. We performed the molecular dynamics (MD) simulation in an explicit solvent to investigate the molecular mechanisms of noscapine for stable binding and conformational changes to the main protease (Mpro) of SARS-CoV-2. The drug repurposing study revealed the high potential of noscapine and proximal binding to the Mpro enzyme in a comparative binding pattern analyzed with chloroquine, ribavirin, and favipiravir. Noscapine binds closely to binding pocket-3 of the Mpro enzyme and depicted stable binding with RMSD 0.1\u20131.9 \u00c5 and RMSF profile peak conformational fluctuations at 202\u2013306 residues, and a Rg score ranging from 21.9 to 22.4 \u00c5. The MM\/PB (GB) SA calculation landscape revealed the most significant contribution in terms of binding energy with \u0394PB \u221219.08 and \u0394GB \u221227.17 kcal\/mol. The electrostatic energy distribution in MM energy was obtained to be \u221271.16 kcal\/mol and depicted high free energy decomposition (electrostatic energy) at 155\u2013306 residues (binding pocket-3) of Mpro by a MM force field. Moreover, the dynamical residue cross-correlation map also stated that the high pairwise correlation occurred at binding residues 200\u2013306 of the Mpro enzyme (binding pocket-3) with noscapine. Principal component analysis depicted the enhanced movement of protein atoms with a high number of static hydrogen bonds. The obtained binding results of noscapine were also well correlated with the pharmacokinetic parameters of antiviral drugs.<\/jats:p>","DOI":"10.1021\/acs.jproteome.0c00367","type":"journal-article","created":{"date-parts":[[2020,8,6]],"date-time":"2020-08-06T11:03:51Z","timestamp":1596711831000},"page":"4678-4689","source":"Crossref","is-referenced-by-count":47,"title":["Molecular Binding\nMechanism and Pharmacology Comparative\nAnalysis of Noscapine for Repurposing against SARS-CoV\u20112 Protease"],"prefix":"10.1021","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9348-458X","authenticated-orcid":true,"given":"Neeraj","family":"Kumar","sequence":"first","affiliation":[{"name":"University of Delhi , , ,","place":["Delhi, India, 110007"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7636-4845","authenticated-orcid":true,"given":"Damini","family":"Sood","sequence":"additional","affiliation":[{"name":"University of Delhi , , ,","place":["Delhi, India, 110007"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter J.","family":"van der Spek","sequence":"additional","affiliation":[{"name":"University Medical Center , , ,","place":["Rotterdam, The Netherlands, 3015GD"]},{"name":"Erasmus Center for Data Analysis (ECDA) , ,","place":["Rotterdam, The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hari S.","family":"Sharma","sequence":"additional","affiliation":[{"name":"University Medical Center , , ,","place":["Rotterdam, The Netherlands, 3015GD"]},{"name":"Erasmus Center for Data Analysis (ECDA) , ,","place":["Rotterdam, The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2993-3560","authenticated-orcid":true,"given":"Ramesh","family":"Chandra","sequence":"additional","affiliation":[{"name":"University of Delhi , , ,","place":["Delhi, India, 110007"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2020,8,6]]},"reference":[{"key":"2026081714260945200_cit1","unstructured":"Coronavirus COVID-19\nGlobal Cases by the Center for Systems Science\nand Engineering (CSSE) at John Hopkins University & Medicine:\nCoronavirus Resource Center. https:\/\/coronavirus.jhu.edu\/map.html."},{"key":"2026081714260945200_cit2","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1021\/acscentsci.0c00272","article-title":"Research and\nDevelopment on Therapeutic\nAgents and Vaccines for COVID-19 and Related Human Coronavirus Diseases","volume":"6","author":"Liu","year":"2020","journal-title":"ACS Cent. Sci."},{"key":"2026081714260945200_cit3","volume-title":"Coronavirus\nDisease (COVID-19) Pandemic Statics"},{"key":"2026081714260945200_cit200","doi-asserted-by":"crossref","first-page":"572","DOI":"10.7861\/clinmedicine.9-6-572","article-title":"Prevention is better than cure","volume":"9","author":"Borysiewicz","year":"2009","journal-title":"Clin. Med. (Lond)."},{"key":"2026081714260945200_cit4","doi-asserted-by":"publisher","first-page":"230","DOI":"10.1111\/imr.12098","article-title":"Advances\nin antiviral vaccine development","volume":"255","author":"Graham","year":"2013","journal-title":"Immunol. Rev."},{"key":"2026081714260945200_cit5","doi-asserted-by":"publisher","first-page":"105924","DOI":"10.1016\/j.ijantimicag.2020.105924","article-title":"Severe\nacute respiratory syndrome coronavirus 2 (SARS-CoV-2) and corona virus\ndisease-2019 (COVID-19): the epidemic and the challenges","volume":"55","author":"Lai","year":"2020","journal-title":"Int. J. Antimicrob. Agents"},{"key":"2026081714260945200_cit6","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1038\/d41587-020-00003-1","article-title":"Coronavirus\nputs drug repurposing on the fast track","volume":"38","author":"Harrison","year":"2020","journal-title":"Nat.\nBiotechnol."},{"key":"2026081714260945200_cit7","doi-asserted-by":"publisher","first-page":"461","DOI":"10.1089\/088282403771926292","article-title":"SARS: lessons learned from other coronaviruses","volume":"16","author":"Navas-Martin","year":"2003","journal-title":"Viral Immunol."},{"key":"2026081714260945200_cit8","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1006\/viro.2000.0757","article-title":"Coronavirus Spike Proteins in Viral\nEntry and Pathogenesis","volume":"279","author":"Gallagher","year":"2001","journal-title":"Virology"},{"key":"2026081714260945200_cit9","doi-asserted-by":"publisher","first-page":"707","DOI":"10.1001\/jama.2020.0757","article-title":"Coronavirus\nInfections\ue5f8More\nThan Just the Common Cold","volume":"323","author":"Paules","year":"2020","journal-title":"JAMA"},{"key":"2026081714260945200_cit10","doi-asserted-by":"publisher","first-page":"5187","DOI":"10.1158\/1078-0432.CCR-04-0360","article-title":"Noscapine\ncrosses the blood-brain barrier and inhibits glioblastoma growth","volume":"10","author":"Landen","year":"2004","journal-title":"Clin. Cancer Res."},{"key":"2026081714260945200_cit11","unstructured":"Acuff, C.; Kalman, D.\n          Noscapine\nand\nNoscapine Analogs and Their Use in treating Infectious Diseases by\nTubulin Binding Inhibition. United States Patent Application 20110274651-A1; 11\/10\/2011; Emory University, Atlanta, GA. http:\/\/www.freepatentsonline.com\/20110274651.pdf."},{"key":"2026081714260945200_cit12","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1111\/j.2042-7166.2003.tb05815.x","article-title":"Antiviral agents from\nplants and herbs: a systematic review","volume":"8","author":"Martin","year":"2003","journal-title":"Antivir.\nTher."},{"key":"2026081714260945200_cit13","doi-asserted-by":"publisher","first-page":"24","DOI":"10.4103\/2225-4110.124335","article-title":"Antiviral Natural Products and Herbal\nMedicines. J. Tradit. Complement.","volume":"4","author":"Lin","year":"2014","journal-title":"Med."},{"key":"2026081714260945200_cit14","doi-asserted-by":"publisher","first-page":"696","DOI":"10.3390\/biom9110696","article-title":"Natural Bis-Benzylisoquinoline\nAlkaloids-Tetrandrine, Fangchinoline,\nand Cepharanthine, Inhibit Human Coronavirus OC43 Infection of MRC-5\nHuman Lung Cells","volume":"9","author":"Kim","year":"2019","journal-title":"Biomolecules"},{"key":"2026081714260945200_cit15","doi-asserted-by":"publisher","first-page":"4892","DOI":"10.1002\/slct.201803360","article-title":"Theoretical Model\nto Study the Interaction of Erythro-Noscapines\nwith nsP3 protease of Chikungunya Virus","volume":"4","author":"Kumar","year":"2019","journal-title":"Chemistry\nSelect"},{"key":"2026081714260945200_cit16","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2019.e02795","article-title":"Computational approach to study the synthesis of noscapine\nand potential of stereoisomers against nsP3 protease of CHIKV","volume":"5","author":"Singh","year":"2019","journal-title":"Heliyon"},{"key":"2026081714260945200_cit17","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1007\/s002620000109","article-title":"Noscapine inhibits tumor growth with little toxicity\nto normal tissues or inhibition of immune responses","volume":"49","author":"Ke","year":"2000","journal-title":"Cancer Immunol. Immunother."},{"key":"2026081714260945200_cit18","doi-asserted-by":"publisher","first-page":"1072","DOI":"10.1002\/med.21357","article-title":"The Noscapine\nChronicle: A Pharmaco-Historic Biography of the Opiate Alkaloid Family\nand its Clinical Applications","volume":"35","author":"Rida","year":"2015","journal-title":"Med. Res. Rev."},{"key":"2026081714260945200_cit19","doi-asserted-by":"publisher","first-page":"2056","DOI":"10.2174\/1568026619666181129125524","article-title":"Designing\nof a Novel Indoline Scaffold\nBased Antibacterial Compound and Pharmacological Evaluation Using\nChemoinformatics Approach","volume":"18","author":"Singh","year":"2019","journal-title":"Curr. Top. Med. Chem."},{"key":"2026081714260945200_cit20","doi-asserted-by":"publisher","first-page":"44","DOI":"10.5808\/GI.2018.16.3.44","article-title":"Antibacterial and Pharmacological\nEvaluation of Fluoroquinolones: A Chemoinformatics Approach","volume":"16","author":"Sood","year":"2018","journal-title":"Genomics Inf."},{"key":"2026081714260945200_cit21","doi-asserted-by":"publisher","first-page":"1288","DOI":"10.1080\/21691401.2017.1369423","article-title":"Preclinical evaluation and molecular docking of 1,3-\nbenzodioxole propargyl ether derivatives as novel inhibitor for combating\nthe histone deacetylase enzyme in cancer. Artif. Cells, Nanomed","volume":"46","author":"Kumar","year":"2018","journal-title":"Artif. Cells, Nanomed., Biotechnol."},{"key":"2026081714260945200_cit22","doi-asserted-by":"publisher","first-page":"1335","DOI":"10.1080\/07391102.2019.1604266","article-title":"4-Bromo-4\u2032-chloro\npyrazoline analog of curcumin augmented\nanticancer activity against human cervical cancer, HeLa cells: in\nsilico-guided analysis, synthesis, and in vitro cytotoxicity","volume":"38","author":"Chaudhary","year":"2020","journal-title":"J. Biomol. Struct. Dyn."},{"key":"2026081714260945200_cit23","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1080\/07391102.2019.1578264","article-title":"Chloro and bromo-pyrazole curcumin Knoevenagel condensates\naugmented anticancer activity against human cervical cancer cells:\ndesign, synthesis, in silico docking and in vitro cytotoxicity analysis","volume":"38","author":"Chaudhary","year":"2020","journal-title":"J. Biomol. Struct. Dyn."},{"key":"2026081714260945200_cit24","doi-asserted-by":"publisher","first-page":"69","DOI":"10.3389\/fbioe.2016.00069","article-title":"A Novel Peptide\nThrombopoietin Mimetic Designing and Optimization Using Computational\nApproach","volume":"4","author":"Singh","year":"2016","journal-title":"Front. Bioeng. Biotechnol."},{"key":"2026081714260945200_cit25","doi-asserted-by":"publisher","first-page":"16964","DOI":"10.1038\/s41598-018-35384-6","article-title":"Mechanistic Interaction\nStudy of Bromo-Noscapine with\nBovine Serum Albumin employing Spectroscopic and Chemo- informatics\nApproaches","volume":"8","author":"Sood","year":"2018","journal-title":"Sci. Rep."},{"key":"2026081714260945200_cit26","doi-asserted-by":"publisher","first-page":"16233","DOI":"10.1021\/acsomega.9b02578","article-title":"Deciphering the Binding Mechanism\nof Noscapine with\nLysozyme: Biophysical and Chemoinformatic Approaches","volume":"4","author":"Sood","year":"2019","journal-title":"ACS Omega"},{"key":"2026081714260945200_cit27","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1021\/acs.jcim.9b01051","article-title":"Multiepitope\nSubunit\nVaccine to Evoke Immune Response against Acute Encephalitis","volume":"60","author":"Kumar","year":"2020","journal-title":"J. Chem. Inf. Model."},{"key":"2026081714260945200_cit28","doi-asserted-by":"publisher","first-page":"2515","DOI":"10.1128\/JVI.02114-07","article-title":"Structures of Two Coronavirus\nMain Proteases: Implications for Substrate Binding and Antiviral Drug\nDesign","volume":"82","author":"Xue","year":"2008","journal-title":"J. Virol."},{"key":"2026081714260945200_cit29","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1107\/S0021889892009944","article-title":"PROCHECK: a program\nto check the stereochemical quality of protein structures","volume":"26","author":"Laskowski","year":"1993","journal-title":"J. Appl. Crystallogr."},{"key":"2026081714260945200_cit30","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1002\/prot.340120407","article-title":"Stereochemical quality\nof protein structure coordinates","volume":"12","author":"Morris","year":"1992","journal-title":"Proteins:\nStruct., Funct., Genet."},{"key":"2026081714260945200_cit31","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1016\/0263-7855(90)80070-V","article-title":"What if: A\nmolecular modelling an drug design program","volume":"8","author":"Vriend","year":"1990","journal-title":"J. Mol. Graphics"},{"key":"2026081714260945200_cit32","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1016\/j.dsx.2020.03.011","article-title":"Chloroquine\nand hydroxychloroquine in the treatment of COVID-19 with or without\ndiabetes: A systematic search and a narrative review with a special\nreference to India and other developing countries","volume":"14","author":"Singh","year":"2020","journal-title":"Diabetes Metab Syndr."},{"key":"2026081714260945200_cit33","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1093\/jac\/dkn243","article-title":"The management of coronavirus infections\nwith particular\nreference to SARS","volume":"62","author":"Wong","year":"2008","journal-title":"J. Antimicrob. Chemother."},{"key":"2026081714260945200_cit34","doi-asserted-by":"publisher","first-page":"W445","DOI":"10.1093\/nar\/gkq311","article-title":"HexServer:\nan FFT-based protein docking server powered by graphics processors","volume":"38","author":"Macindoe","year":"2010","journal-title":"Nucleic Acids Res."},{"key":"2026081714260945200_cit35","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1002\/pro.3289","article-title":"PDBsum: Structural summaries of PDB entries","volume":"27","author":"Laskowski","year":"2018","journal-title":"Protein Sci."},{"key":"2026081714260945200_cit36","doi-asserted-by":"publisher","first-page":"2778","DOI":"10.1021\/ci200227u","article-title":"LigPlot+: multiple ligand-protein interaction diagrams\nfor drug discovery","volume":"51","author":"Laskowski","year":"2011","journal-title":"J. Chem. Inf. Model."},{"key":"2026081714260945200_cit37","doi-asserted-by":"publisher","DOI":"10.1093\/bib\/bbz141","article-title":"LARMD:\nintegration of bioinformatic resources to profile ligand-driven protein\ndynamics with a case on the activation of estrogen receptor","author":"Yang","year":"2019","journal-title":"Briefings Bioinf."},{"key":"2026081714260945200_cit38","doi-asserted-by":"publisher","first-page":"2695","DOI":"10.1093\/bioinformatics\/btl461","article-title":"Bio3d:\nan R package for the comparative analysis of protein structures","volume":"22","author":"Grant","year":"2006","journal-title":"Bioinformatics"},{"key":"2026081714260945200_cit39","doi-asserted-by":"publisher","first-page":"1528","DOI":"10.1016\/j.bpj.2015.08.015","article-title":"MDTraj: A Modern\nOpen Library for the Analysis of Molecular\nDynamics Trajectories","volume":"109","author":"McGibbon","year":"2015","journal-title":"Biophys. J."},{"key":"2026081714260945200_cit40","doi-asserted-by":"publisher","first-page":"4066","DOI":"10.1021\/acs.jmedchem.5b00104","article-title":"pkCSM:\nPredicting Small-Molecule\nPharmacokinetic and Toxicity Properties Using Graph-Based Signatures","volume":"58","author":"Pires","year":"2015","journal-title":"J. Med. Chem."},{"key":"2026081714260945200_cit41","doi-asserted-by":"publisher","first-page":"42717","DOI":"10.1038\/srep42717","article-title":"SwissADME: a free web\ntool to evaluate\npharmacokinetics, drug-likeness and medicinal chemistry friendliness\nof small molecules","volume":"7","author":"Daina","year":"2017","journal-title":"Sci. Rep."}],"container-title":["Journal of Proteome Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acs.jproteome.0c00367","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/jprobs\/article-pdf\/19\/11\/4678\/14424094\/pr0c00367.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/jprobs\/article-pdf\/19\/11\/4678\/14424094\/pr0c00367.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T18:26:21Z","timestamp":1786991181000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/jprobs\/article\/19\/11\/4678\/1383672\/Molecular-Binding-Mechanism-and-Pharmacology"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,8,6]]},"references-count":42,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2020,8,6]]},"published-print":{"date-parts":[[2020,11,6]]}},"URL":"https:\/\/doi.org\/10.1021\/acs.jproteome.0c00367","relation":{},"ISSN":["1535-3893","1535-3907"],"issn-type":[{"value":"1535-3893","type":"print"},{"value":"1535-3907","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,8,6]]}}}