{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T17:12:54Z","timestamp":1783444374764,"version":"3.54.6"},"reference-count":43,"publisher":"Royal Society of Chemistry (RSC)","issue":"44","license":[{"start":{"date-parts":[[2020,9,30]],"date-time":"2020-09-30T00:00:00Z","timestamp":1601424000000},"content-version":"vor","delay-in-days":273,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/3.0\/"}],"funder":[{"name":"Bristol-Myers Squibb"},{"DOI":"10.13039\/100006369","name":"George Mason University","doi-asserted-by":"crossref","award":["PD45722"],"award-info":[{"award-number":["PD45722"]}],"id":[{"id":"10.13039\/100006369","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100004948","name":"Michigan Economic Development Corporation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100004948","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100004319","name":"Pfizer","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100004319","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["GM126189"],"award-info":[{"award-number":["GM126189"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"name":"National Science Foundation","award":["DMS-1721024"],"award-info":[{"award-number":["DMS-1721024"]}]},{"name":"National Science Foundation","award":["DMS-1761320"],"award-info":[{"award-number":["DMS-1761320"]}]},{"name":"National Science Foundation","award":["IIS1900473"],"award-info":[{"award-number":["IIS1900473"]}]}],"content-domain":{"domain":["rsc.org"],"crossmark-restriction":true},"short-container-title":["Chem. Sci."],"abstract":"<p>By integrating algebraic topology and deep learning, we provide a reliable ranking of binding affinities, binding site analysis, and fragment decomposition for 137 SARS-CoV-2 main protease inhibitors.<\/p>","DOI":"10.1039\/d0sc04641h","type":"journal-article","created":{"date-parts":[[2020,9,30]],"date-time":"2020-09-30T09:16:51Z","timestamp":1601457411000},"page":"12036-12046","update-policy":"https:\/\/doi.org\/10.1039\/rsc_crossmark_policy","source":"Crossref","is-referenced-by-count":75,"title":["Unveiling the molecular mechanism of SARS-CoV-2 main protease inhibition from 137 crystal structures using algebraic topology and deep learning"],"prefix":"10.1039","volume":"11","author":[{"given":"Duc Duy","family":"Nguyen","sequence":"first","affiliation":[{"name":"Department of Mathematics"},{"name":"University of Kentucky"},{"name":"USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaifu","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Mathematics"},{"name":"Michigan State University"},{"name":"USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiahui","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Mathematics"},{"name":"Michigan State University"},{"name":"USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Mathematics"},{"name":"Michigan State University"},{"name":"USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8132-5998","authenticated-orcid":false,"given":"Guo-Wei","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Mathematics"},{"name":"Michigan State University"},{"name":"USA"},{"name":"Department of Biochemistry and Molecular Biology"},{"name":"Michigan State University"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"292","published-online":{"date-parts":[[2020]]},"reference":[{"key":"D0SC04641H-(cit1)\/*[position()=1]","volume-title":"Phase III Double-blind, Placebo-controlled Study of AZD1222 for the Prevention of COVID-19 in Adults","year":"2020","unstructured":"Phase III Double-blind, Placebo-controlled Study of AZD1222 for the Prevention of COVID-19 in Adults , 2020 , accessed September 15, 2020, https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04516746?term=NCT04516746&draw=2&rank=1"},{"key":"D0SC04641H-(cit2)\/*[position()=1]","volume-title":"Statement on AstraZeneca Oxford SARS-CoV-2 vaccine, AZD1222, COVID-19 vaccine trials temporary pause","year":"2020","unstructured":"Statement on AstraZeneca Oxford SARS-CoV-2 vaccine, AZD1222, COVID-19 vaccine trials temporary pause , 2020 , accessed September 15, 2020, https:\/\/www.astrazeneca.com\/media-centre\/press-releases\/2020\/statement-on-astrazeneca-oxford-sars-cov-2-vaccine-azd1222-covid-19-vaccine-trials-temporary-pause.html"},{"issue":"3","key":"D0SC04641H-(cit3)\/*[position()=1]","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1007\/s11427-020-1637-5","volume":"63","author":"Xu","year":"2020","journal-title":"Sci. China: Life Sci."},{"issue":"W1","key":"D0SC04641H-(cit4)\/*[position()=1]","doi-asserted-by":"crossref","first-page":"W612","DOI":"10.1093\/nar\/gkv352","volume":"43","author":"Davies","year":"2015","journal-title":"Nucleic Acids Res."},{"issue":"1","key":"D0SC04641H-(cit5)\/*[position()=1]","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1093\/nar\/28.1.235","volume":"28","author":"Berman","year":"2000","journal-title":"Nucleic Acids Res."},{"key":"D0SC04641H-(cit6)\/*[position()=1]","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1007\/s10822-019-00237-5","volume":"34","author":"Nguyen","year":"2020","journal-title":"J. Comput.-Aided Mol. Des."},{"issue":"20","key":"D0SC04641H-(cit7)\/*[position()=1]","doi-asserted-by":"crossref","first-page":"11000","DOI":"10.1073\/pnas.96.20.11000","volume":"96","author":"Matthews","year":"1999","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"issue":"10","key":"D0SC04641H-(cit8)\/*[position()=1]","doi-asserted-by":"crossref","first-page":"e324","DOI":"10.1371\/journal.pbio.0030324","volume":"3","author":"Yang","year":"2005","journal-title":"PLoS Biol."},{"issue":"16","key":"D0SC04641H-(cit9)\/*[position()=1]","doi-asserted-by":"crossref","first-page":"4971","DOI":"10.1021\/jm0603926","volume":"49","author":"Yang","year":"2006","journal-title":"J. Med. Chem."},{"key":"D0SC04641H-(cit10)\/*[position()=1]","doi-asserted-by":"crossref","first-page":"22677","DOI":"10.1038\/srep22677","volume":"6","author":"Wang","year":"2016","journal-title":"Sci. Rep."},{"key":"D0SC04641H-(cit11)\/*[position()=1]","author":"Jin","year":"2020","journal-title":"bioRxiv"},{"issue":"557","key":"D0SC04641H-(cit12)\/*[position()=1]","doi-asserted-by":"crossref","first-page":"eabc5332","DOI":"10.1126\/scitranslmed.abc5332","volume":"12","author":"Rathnayake","year":"2020","journal-title":"Sci. Transl. Med."},{"key":"D0SC04641H-(cit14)\/*[position()=1]","doi-asserted-by":"crossref","first-page":"1444","DOI":"10.1002\/jcc.25213","volume":"39","author":"Wu","year":"2018","journal-title":"J. Comput. Chem."},{"issue":"4","key":"D0SC04641H-(cit15)\/*[position()=1]","doi-asserted-by":"crossref","first-page":"1374","DOI":"10.1529\/biophysj.106.091736","volume":"92","author":"Chang","year":"2007","journal-title":"Biophys. J."},{"issue":"4","key":"D0SC04641H-(cit16)\/*[position()=1]","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1038\/nrd3408","volume":"10","author":"Park","year":"2011","journal-title":"Nat. Rev. Drug Discovery"},{"issue":"10","key":"D0SC04641H-(cit17)\/*[position()=1]","doi-asserted-by":"crossref","first-page":"1503","DOI":"10.1002\/cmdc.200800178","volume":"3","author":"Degen","year":"2008","journal-title":"ChemMedChem"},{"key":"D0SC04641H-(cit18)\/*[position()=1]","author":"Su","year":"2018","journal-title":"J. Chem. Inf. Model."},{"issue":"6489","key":"D0SC04641H-(cit19)\/*[position()=1]","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1126\/science.abb3405","volume":"368","author":"Zhang","year":"2020","journal-title":"Science"},{"key":"D0SC04641H-(cit20)\/*[position()=1]","author":"Su","year":"2020","journal-title":"bioRxiv"},{"issue":"10","key":"D0SC04641H-(cit21)\/*[position()=1]","doi-asserted-by":"crossref","first-page":"5871","DOI":"10.1021\/acscatal.0c00110","volume":"10","author":"Wang","year":"2020","journal-title":"ACS Catal."},{"issue":"6497","key":"D0SC04641H-(cit22)\/*[position()=1]","doi-asserted-by":"crossref","first-page":"1331","DOI":"10.1126\/science.abb4489","volume":"368","author":"Dai","year":"2020","journal-title":"Science"},{"key":"D0SC04641H-(cit23)\/*[position()=1]","author":"Ma","year":"2020","journal-title":"bioRxiv"},{"key":"D0SC04641H-(cit24)\/*[position()=1]","doi-asserted-by":"crossref","first-page":"5047","DOI":"10.1038\/s41467-020-18709-w","volume":"11","author":"Douangamath","year":"2020","journal-title":"Nat. Commun."},{"issue":"1","key":"D0SC04641H-(cit25)\/*[position()=1]","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1111\/j.1747-0285.2008.00679.x","volume":"72","author":"Bacha","year":"2008","journal-title":"Chem. Biol. Drug Des."},{"issue":"11","key":"D0SC04641H-(cit26)\/*[position()=1]","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1002\/cmdc.202000223","volume":"15","author":"Ghosh","year":"2020","journal-title":"ChemMedChem"},{"issue":"4","key":"D0SC04641H-(cit27)\/*[position()=1]","doi-asserted-by":"crossref","first-page":"361","DOI":"10.2174\/156802606776287090","volume":"6","author":"Liang","year":"2006","journal-title":"Curr. Top. Med. Chem."},{"issue":"5","key":"D0SC04641H-(cit28)\/*[position()=1]","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1517\/13543776.17.5.533","volume":"17","author":"Wang","year":"2007","journal-title":"Expert Opin. Ther. Pat."},{"issue":"10","key":"D0SC04641H-(cit29)\/*[position()=1]","doi-asserted-by":"crossref","first-page":"1337","DOI":"10.1517\/13543776.2013.823159","volume":"23","author":"Kumar","year":"2013","journal-title":"Expert Opin. Ther. Pat."},{"issue":"14","key":"D0SC04641H-(cit30)\/*[position()=1]","doi-asserted-by":"crossref","first-page":"6595","DOI":"10.1021\/acs.jmedchem.5b01461","volume":"59","author":"Pillaiyar","year":"2016","journal-title":"J. Med. Chem."},{"key":"D0SC04641H-(cit31)\/*[position()=1]","doi-asserted-by":"crossref","first-page":"127377","DOI":"10.1016\/j.bmcl.2020.127377","author":"Ullrich","year":"2020","journal-title":"Bioorg. Med. Chem. Lett."},{"issue":"1","key":"D0SC04641H-(cit32)\/*[position()=1]","doi-asserted-by":"publisher","first-page":"e1005929","DOI":"10.1371\/journal.pcbi.1005929","volume":"14","author":"Cang","year":"2018","journal-title":"PLoS Comput. Biol."},{"issue":"7","key":"D0SC04641H-(cit33)\/*[position()=1]","doi-asserted-by":"crossref","first-page":"3291","DOI":"10.1021\/acs.jcim.9b00334","volume":"59","author":"Nguyen","year":"2019","journal-title":"J. Chem. Inf. Model."},{"issue":"2","key":"D0SC04641H-(cit34)\/*[position()=1]","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1090\/S0273-0979-09-01249-X","volume":"46","author":"Carlsson","year":"2009","journal-title":"Bull. Am. Math. Soc."},{"issue":"3","key":"D0SC04641H-(cit35)\/*[position()=1]","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1006\/jmbi.1996.0897","volume":"267","author":"Jones","year":"1997","journal-title":"J. Mol. Biol."},{"issue":"2","key":"D0SC04641H-(cit36)\/*[position()=1]","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1002\/jcc.21334","volume":"31","author":"Trott","year":"2010","journal-title":"J. Comput. Chem."},{"issue":"7","key":"D0SC04641H-(cit37)\/*[position()=1]","doi-asserted-by":"crossref","first-page":"1739","DOI":"10.1021\/jm0306430","volume":"47","author":"Friesner","year":"2004","journal-title":"J. Med. Chem."},{"key":"D0SC04641H-(cit38)\/*[position()=1]","volume-title":"Development of a protein-ligand extended connectivity (plec) fingerprint and its application for binding affinity predictions","author":"W\u00f3jcikowski","year":"2018","unstructured":"M. W\u00f3jcikowski , M.Kukie\u0142ka , M.Stepniewska-Dziubinska and P.Siedlecki , Development of a protein-ligand extended connectivity (plec) fingerprint and its application for binding affinity predictions , 2018"},{"issue":"3","key":"D0SC04641H-(cit39)\/*[position()=1]","doi-asserted-by":"crossref","first-page":"e3179","DOI":"10.1002\/cnm.3179","volume":"35","author":"Nguyen","year":"2019","journal-title":"Int. J. Numer. Method Biomed. Eng."},{"issue":"14","key":"D0SC04641H-(cit40)\/*[position()=1]","doi-asserted-by":"crossref","first-page":"15956","DOI":"10.1021\/acsomega.9b01997","volume":"4","author":"Zheng","year":"2019","journal-title":"ACS Omega"},{"key":"D0SC04641H-(cit41)\/*[position()=1]","first-page":"e1465","author":"Li","year":"2020","journal-title":"Wiley Interdiscip. Rev.: Comput. Mol. Sci."},{"issue":"8","key":"D0SC04641H-(cit42)\/*[position()=1]","doi-asserted-by":"crossref","first-page":"4343","DOI":"10.1039\/C9CP06554G","volume":"22","author":"Nguyen","year":"2020","journal-title":"Phys. Chem. Chem. Phys."},{"issue":"2","key":"D0SC04641H-(cit43)\/*[position()=1]","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1021\/acs.jcim.7b00650","volume":"58","author":"Jim\u00e9nez","year":"2018","journal-title":"J. Chem. Inf. Model."},{"key":"D0SC04641H-(cit44)\/*[position()=1]","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1021\/acs.jcim.7b00558","volume":"58","author":"Wu","year":"2018","journal-title":"J. Chem. Inf. Model."}],"container-title":["Chemical Science"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/pubs.rsc.org\/en\/content\/articlepdf\/2020\/SC\/D0SC04641H","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/pubs.rsc.org\/en\/content\/articlepdf\/2020\/SC\/D0SC04641H","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T20:43:48Z","timestamp":1782852228000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.rsc.org\/sc\/article\/11\/44\/12036-12046\/706130"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020]]},"references-count":43,"journal-issue":{"issue":"44","published-print":{"date-parts":[[2020,11,18]]}},"URL":"https:\/\/doi.org\/10.1039\/d0sc04641h","relation":{},"ISSN":["2041-6520","2041-6539"],"issn-type":[{"value":"2041-6520","type":"print"},{"value":"2041-6539","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020]]},"assertion":[{"value":"This document is Similarity Check deposited","name":"similarity_check","explanation":{"URL":"https:\/\/www.crossref.org\/services\/similarity-check\/"},"group":{"name":"similarity_check","label":"SIMILARITY CHECK"}},{"value":"Supplementary Information","URL":"https:\/\/doi.org\/10.1039\/D0SC04641H","name":"related_data","group":{"name":"related_data","label":"RELATED DATA"}},{"value":"Guo-Wei Wei (ORCID)","URL":"http:\/\/orcid.org\/0000-0001-8132-5998","name":"identifier","group":{"name":"author_identifiers","label":"IDENTIFIERS"}},{"value":"Single-blind","order":2,"name":"peer_review_method","group":{"name":"peer_review_method","label":"PEER REVIEW METHOD"}},{"value":"Received 21 August 2020; Accepted 30 September 2020; Accepted Manuscript published 30 September 2020; Advance Article published 21 October 2020; Version of Record published 18 November 2020","order":1,"name":"history","group":{"name":"publication_history","label":"PUBLICATION HISTORY"}}]}}