{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T04:21:16Z","timestamp":1777522876152,"version":"3.51.4"},"reference-count":33,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2020,5,31]],"date-time":"2020-05-31T00:00:00Z","timestamp":1590883200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Computation"],"abstract":"<jats:p>Since the outbreak of the 2019 novel coronavirus disease (COVID-19), the medical research community is vigorously seeking a treatment to control the infection and save the lives of severely infected patients. The main potential candidates for the control of viruses are virally targeted agents. In this short letter, we report our calculations on the inhibitors for the SARS-CoV-2 3CL protease and the spike protein for the potential treatment of COVID-19. The results show that the most potent inhibitors of the SARS-CoV-2 3CL protease include saquinavir, tadalafil, rivaroxaban, sildenafil, dasatinib, etc. Ergotamine, amphotericin b, and vancomycin are most promising to block the interaction of the SARS-CoV-2 S-protein with human ACE-2.<\/jats:p>","DOI":"10.3390\/computation8020053","type":"journal-article","created":{"date-parts":[[2020,6,1]],"date-time":"2020-06-01T11:49:21Z","timestamp":1591012161000},"page":"53","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Computational View toward the Inhibition of SARS-CoV-2 Spike Glycoprotein and the 3CL Protease"],"prefix":"10.3390","volume":"8","author":[{"given":"Zhen","family":"Qiao","sequence":"first","affiliation":[{"name":"Department of Orthopaedics, The Warren Alpert Medical School of Brown University, Rhode Island Hospital, Providence, RI 02903, USA"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9173-0049","authenticated-orcid":false,"given":"Hongtao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Departments of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19301, USA"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5450-0121","authenticated-orcid":false,"given":"Hai-Feng","family":"Ji","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Drexel University, Philadelphia, PA 19104, USA"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4406-5618","authenticated-orcid":false,"given":"Qian","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics, The Warren Alpert Medical School of Brown University, Rhode Island Hospital, Providence, RI 02903, USA"}]}],"member":"1968","published-online":{"date-parts":[[2020,5,31]]},"reference":[{"key":"ref_1","first-page":"30251","article-title":"Genomic characterisation and epidemiology of 2019 novel coronavirus: Implications for virus origins and receptor binding","volume":"20","author":"Lu","year":"2020","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1038\/s41586-020-2012-7","article-title":"A pneumonia outbreak associated with a new coronavirus of probable bat origin","volume":"579","author":"Zhou","year":"2020","journal-title":"Nature"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1146\/annurev-virology-110615-042301","article-title":"Structure, Function, and Evolution of Coronavirus Spike Proteins","volume":"3","author":"Li","year":"2016","journal-title":"Annu. Rev. Virol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1007\/s11427-020-1637-5","article-title":"Evolution of the novel coronavirus from the ongoing Wuhan outbreak and modeling of its spike protein for risk of human transmission","volume":"63","author":"Xu","year":"2020","journal-title":"Sci. China Life Sci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1136\/thorax.2003.012658","article-title":"Role of lopinavir\/ritonavir in the treatment of SARS: Initial virological and clinical findings","volume":"59","author":"Chu","year":"2004","journal-title":"Thorax"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1016\/j.jtbi.2008.07.030","article-title":"Molecular dynamic simulations analysis of ritonavir and lopinavir as SARS-CoV 3CL(pro) inhibitors","volume":"254","author":"Nukoolkarn","year":"2008","journal-title":"J. Theor. Biol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Liu, X., Zhang, B., Jin, Z., Yang, H., and Rao, Z. (2020). The crytal structure of 2019-nCoV main protease in complex with an inhibitor N3. Nature.","DOI":"10.2210\/pdb6lu7\/pdb"},{"key":"ref_8","first-page":"57","article-title":"Python: A programming language for software integration and development","volume":"17","author":"Sanner","year":"1999","journal-title":"J. Mol. Graph. Model."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1002\/jcc.20084","article-title":"UCSF Chimera\u2014A visualization system for exploratory research and analysis","volume":"25","author":"Pettersen","year":"2004","journal-title":"J. Comput. Chem."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Hanwell, M.D., Curtis, D.E., Lonie, D.C., Vandermeersch, T., Zurek, E., and Hutchison, G.R. (2012). Avogadro: An advanced semantic chemical editor, visualization, and analysis platform. J. Cheminform., 4.","DOI":"10.1186\/1758-2946-4-17"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2785","DOI":"10.1002\/jcc.21256","article-title":"Automated docking with selective receptor flexibility","volume":"16","author":"Morris","year":"2009","journal-title":"J. Comput. Chem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1002\/jcc.21334","article-title":"AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization and multithreading","volume":"31","author":"Trott","year":"2010","journal-title":"J. Comput. Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1006\/jmbi.1993.1626","article-title":"Comparative Protein Modelling by Satisfaction of Spatial Restraints","volume":"234","author":"Blundell","year":"1993","journal-title":"J. Mol. Biol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1107\/S0021889892009944","article-title":"PROCHECK: A program to check the stereochemical quality of protein structures","volume":"26","author":"Laskowski","year":"1993","journal-title":"J. Appl. Cryst."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1646","DOI":"10.1002\/prot.24551","article-title":"Antibody structure determination using a combination of homology modeling, energy-based refinement, and loop prediction","volume":"82","author":"Zhu","year":"2014","journal-title":"Proteins"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1093\/protein\/gzu017","article-title":"Structure-based approach to the prediction of disulfide bonds in proteins","volume":"27","author":"Salam","year":"2014","journal-title":"Protein Eng. Des. Sel."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Beard, H., Cholleti, A., Pearlman, D., Sherman, W., and Loving, K.A. (2013). Applying Physics-Based Scoring to Calculate Free Energies of docking for Single Amino Acid Mutations in Protein-Protein Complexes. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0082849"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2794","DOI":"10.1002\/prot.23106","article-title":"The VSGB 2.0 model: A next generation energy model for high resolution protein structure modeling","volume":"79","author":"Li","year":"2011","journal-title":"Proteins"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1752","DOI":"10.1002\/jcc.20292","article-title":"Integrated Modeling Program, Applied Chemical Theory (IMPACT)","volume":"26","author":"Banks","year":"2005","journal-title":"J. Comput. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"952","DOI":"10.1016\/S0140-6736(95)90699-1","article-title":"Safety and activity of saquinavir in HIV infection","volume":"345","author":"Kitchen","year":"1995","journal-title":"Lancet"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"442","DOI":"10.3762\/bjoc.7.57","article-title":"An Overview of the Key Routes to the Best Selling 5-membered Ring Heterocyclic Pharmaceuticals","volume":"7","author":"Baumann","year":"2011","journal-title":"Beilstein J. Org. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/S0140-6736(08)60880-6","article-title":"Extended duration rivaroxaban versus short-term enoxaparin for the prevention of venous thromboembolism after total hip arthroplasty: A double-blind, randomised controlled trial","volume":"372","author":"Kakkar","year":"2008","journal-title":"Lancet"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1819","DOI":"10.1016\/0960-894X(96)00323-X","article-title":"Sildenafil (Viagra), a potent and selective inhibitor of type 5 cGMP phosphodiesterase with utility for the treatment of male erectile dysfunction","volume":"6","author":"Terrett","year":"1996","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2531","DOI":"10.1056\/NEJMoa055229","article-title":"Dasatinib in imatinib-resistant Philadelphia chromosome-positive leukemias","volume":"354","author":"Talpaz","year":"2006","journal-title":"N. Engl. J. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"42M","DOI":"10.1016\/j.amjcard.2005.07.011","article-title":"Pharmacology and drug interaction effects of the phosphodiesterase 5 inhibitors: Focus on alpha-blocker interactions","volume":"96","author":"Kloner","year":"2005","journal-title":"Am. J. Cardiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/S0009-9236(97)90184-3","article-title":"Montelukast causes prolonged, potent leukotriene D4-receptor antagonism in the airways of patients with asthma","volume":"61","author":"Reiss","year":"1997","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_27","first-page":"1","article-title":"Protease inhibitors\u2019 metabolic side effects: Cholesterol, triglycerides, blood sugar, and \u201cCrix belly. Interview with Lisa Capaldini, M.D. Interview by John S. James\u201d","volume":"277","author":"Capaldini","year":"1997","journal-title":"AIDS Treatment News"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Park, N.H., Shin, K.H., and Kang, M.K. (2017). Chapter 34. Antifungal and Antiviral Agents. Pharmacology and Therapeutics for Dentistry, Elsevier. [7th ed.].","DOI":"10.1016\/B978-0-323-39307-2.00034-5"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1111\/j.1365-2125.1983.tb02243.x","article-title":"Low bioavailability of ergotamine tartrate after oral and rectal administration in migraine sufferers","volume":"16","author":"Ibraheem","year":"1983","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_30","unstructured":"World Health Organization (2010). Control of the Leishmaniasis: Report of a Meeting of the WHO Expert Committee on the Control of Leishmaniases, World Health Organization."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1093\/cid\/cir034","article-title":"Clinical practice guidelines by the infectious diseases society of America for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children: Executive summary","volume":"52","author":"Liu","year":"2011","journal-title":"Clin. Infect. Dis."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1959","DOI":"10.1161\/01.CIR.81.6.1959","article-title":"Carotid sinus baroreceptor sensitivity in experimental heart failure","volume":"81","author":"Wang","year":"1990","journal-title":"Circulation"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1093\/eurheartj\/ehm575","article-title":"New oral anticoagulants in atrial fibrillation","volume":"29","author":"Turpie","year":"2008","journal-title":"Eur. Heart J."}],"container-title":["Computation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-3197\/8\/2\/53\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:34:13Z","timestamp":1760175253000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-3197\/8\/2\/53"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,5,31]]},"references-count":33,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2020,6]]}},"alternative-id":["computation8020053"],"URL":"https:\/\/doi.org\/10.3390\/computation8020053","relation":{},"ISSN":["2079-3197"],"issn-type":[{"value":"2079-3197","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,5,31]]}}}