Virtual Screening of Natural Compounds to Identify Potential Inhibitors of COVID-19 Protease using Molecular Docking
DOI:
https://doi.org/10.37285/ijpsn.2020.13.5.6Abstract
COVID-19 disease has spread quickly across the globe after its first detection in late December 2019 in Wuhan, China. The disease is considered as a potential global health threat by world health organization due to its high emerging deaths. Coronaviruses are transmitted by respiratory aerosols producing mild upper respiratory infections. Currently, no vaccine or specific COVID-19 inhibitors are available for treatment except repurposed drugs. The COVID-19 virus genome has ~30,000 nucleotides. Its replicase gene encodes overlapping polyproteins necessary for viral replication and transcription. Recently COVID-19 main protease was successfully crystallized and made available in Protein Data Bank for public use. Several studies report medicinal plants to have antiviral bioactivities. Application of in silico computer‐based docking studies involving small molecules could be time saving for irrelevant in vivo models. In the present study, we have investigated 500 natural compounds from different plants having antiviral properties. We have also screened several protease inhibitors and other repurposed drugs claimed to be active against COVID-19. The docking was performed on Autodock vina, using grid size 22, 22, 24 along the X, Y, and Z axes with 1.000 A˚ spacing. The docked positions in binding pockets were visualized using Discovery studio 3.5 software. Most of the repurposed protease inhibitors were having good binding energy, saquinavir being the most potent. Among natural compounds, jervine and isoacteoside were found to be having good binding with protease protein. It was observed that flavonoid was the commonest chemical group amongst most potent natural compounds. The amino acids Thr26, Asn142, Gly143, Ser144, Cys145, His163, and Glu166 showed strong H-bond interactions with docked compounds. The conclusion of the recent study will help researchers to identify the better drug to battle COVID-19. To be brief, our findings emphasize a promising pharmaceutical perspective for targeting main protease of novel coronavirus. However further preclinical and clinical trials should be carried out to validate these potential compounds.
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Keywords:
Virtual screening, COVID-19, SARS-COV-2, Flavonoids, Protease Inhibitors, Coronavirus
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Published
2020-09-15
How to Cite
1.
Patel JR, Prajapati LM, Joshi HV, Shah UA. Virtual Screening of Natural Compounds to Identify Potential Inhibitors of COVID-19 Protease using Molecular Docking. Scopus Indexed [Internet]. 2020 Sep. 15 [cited 2024 Dec. 21];13(5):5090-101. Available from: https://ijpsnonline.com/index.php/ijpsn/article/view/1293
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Research Articles
References
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Paraskevis D, Kostaki EG, Magiorkinis G, Panayiotakopoulos G, Sourvinos G and Tsiodras S (2020). Full-genome evolutionary analysis of the novel corona virus (2019-nCoV) rejects the hypothesis of emergence as a result of a recent recombination event. Infect Genet Evol 79: 104212.
Paules CI, Marston HD and Fauci AS (2020). Coronavirus Infections: More than just the common cold. Jama 323(8): 707-708.
Peiris JS, Lai ST, Poon LL, Guan Y, Yam LY, Lim W, Nicholls J, Yee WK, Yan WW, Cheung MT, Cheng VC, Chan KH, Tsang DN, Yung RW, Ng TK and Yuen KY (2003). Coronavirus as a possible cause of severe acute respiratory syndrome. Lancet 361(9366):1319-1325.
Pillaiyar T, Manickam M, Namasivayam V, Hayashi Y, Jung SH (2016). An Overview of Severe Acute Respiratory Syndrome-Coronavirus (SARS-CoV) 3CL Protease Inhibitors: Peptidomimetics and Small Molecule Chemotherapy. J Med Chem 59(14): 6595-628.
Rodríguez-Morales AJ, MacGregor K, Kanagarajah S, Patel D and Schlagenhauf P (2020). Going global – Travel and the 2019 novel coronavirus. Travel Med Infect Dis 33: 101578.
Savarino A, Di Trani L, Donatelli I, Cauda R and Cassone A (2006). New insights into the antiviral effects of chloroquine. Lancet Infect Dis 6(2): 67-9.
Trott O and Olson AJ (2010). AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J Comput Chem 31(2): 455-461.
Wang M, Cao R, Zhang L, Yang X, Liu J, Xu M, Shi Z and Hu Z (2020). Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res 30(3): 269-271.
Wang M, Cao R, Zhang L, Yang X, Liu J, Xu M. Shi Z, Hu Z, Zhong W and Xiao G (2020). Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res 30(3): 269-271.
Weiss SR and Leibowitz JL (2011). Coronavirus pathogenesis. Advances in virus research 81: 85-164.
Wu F, Zhao S, Yu B, Chen Y-M, Wang W, Song Z-G, et al (2020). A new coronavirus associated with human respiratory disease in China. Nature 579(7798): 265-9.
Wu R, Wang L, Kuo H-CD, Shannar A, Peter R, Chou PJ, et al (2020). An Update on Current Therapeutic Drugs Treating COVID-19. Curr Pharmacol Rep 1-15.
Xu Z, Yao H, Shen J, Wu N, Xu Y, Lu X, et al. (2020). Nelfinavir Is Active Against SARS-CoV-2 in Vero E6 Cells. ChemRxiv Preprint 1-4.
Yang H, Yang M, Ding Y, Liu Y, Lou Z, Zhou Z, et al (2003). The crystal structures of severe acute respiratory syndrome virus main protease and its complex with an inhibitor. Proc Natl Acad Sci USA 100(23):13190-5.
Yao X, Ye F, Zhang M, Cui C, Huang B, Niu P, Liu X, Zhao L, Dong E, Song C, Zhan S, Lu R, Li H and Tan W Liu D (2020). In vitro Antiviral Activity and Projection of Optimized Dosing Design of Hydroxychloroquine for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Clin Infect Dis 237.
Zakaryan H, Arabyan E, Oo A and Zandi K (2017). Flavonoids: promising natural compounds against viral infections. Arch Virol 162(9): 2539-2551.
Zhou P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W, et al (2020). A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 579(7798): 270-3.
Anand K, Palm GJ, Mesters JR, Siddell SG, Ziebuhr J and Hilgenfeld R (2002). Structure of coronavirus main proteinase reveals combination of a chymotrypsin fold with an extra alpha-helical domain. EMBO J 21(13): 3213-24.
Baden, LR and Rubin EJ (2020). Covid-19 — The Search for Effective Therapy. New England Journal of Medicine 382(19): 1851-1852.
Ben-Zvi I, Kivity S, Langevitz P and Shoenfeld Y (2012). Hydroxychloroquine: from malaria to autoimmunity. Clin Rev Allergy Immunol 42(2): 145-153.
Boopathi S, Poma AB and Kolandaivel P (2020). Novel 2019 coronavirus structure, mechanism of action, antiviral drug promises and rule out against its treatment. J Biomol Struct Dyn 1-10.
Cao B, Wang Y, Wen D, Liu W, Wang J, Fan G, et al. (2020). A Trial of Lopinavir–Ritonavir in Adults Hospitalized with Severe Covid-19. N Engl J Med 382(19): 1787-1799.
Chen Z, Nakamura T (2004). Statistical evidence for the usefulness of Chinese medicine in the treatment of SARS. Phytother Res 18(7): 592-594.
Cortegiani A, Ingoglia G, Ippolito M, Giarratano A and Einav S (2020). A systematic review on the efficacy and safety of chloroquine for the treatment of COVID-19. J Crit Care S0883-9441(20): 30390-7.
Dannenberg JJ (1998). An Introduction to Hydrogen Bonding By George A. Jeffrey (University of Pittsburgh). Oxford University Press: New York and Oxford. 1997.
Dassault Systèmes BIOVIA, (2017). Discovery Studio Modeling Environment, San Diego: Dassault Systèmes 2016.
de WE, van DN, Falzarano D and Munster VJ (2016). SARS and MERS: recent insights into emerging coronaviruses. Nature reviews Microbiology. Nat Rev Microbiol 14(8): 523-534.
Denaro M and Smeriglio A (2020). Antiviral activity of plants and their isolated bioactive compounds: An update. Phytother Res 34(4): 742-68.
Duke JA (2002). Handbook of Medicinal Herbs, 2nd ed. CRC, New York.
Fehr AR and Perlman S (2015). Coronaviruses: an overview of their replication and pathogenesis. Methods Mol Biol 1282: 1-23.
Fox R (1996). Anti-malarial drugs: possible mechanisms of action in autoimmune disease and prospects for drug development. Lupus 5(1): S4-10.
Fox RI (1993). Mechanism of action of hydroxy-chloroquine as an antirheumatic drug. Semin Arthritis Rheu 23(2): 82-91.
Ganjhu RK, Mudgal PP, Maity H, Dowarha D, Devadiga S, Nag S, et al (2015). Herbal plants and plant preparations as remedial approach for viral diseases. Virusdisease 26(4): 225-36.
Gautret P, Lagier JC, Parola P, Hoang VT, Meddeb L, Mailhe M, Doudier B, Courjon J, Giordanengo V, Vieira VE, Dupont HT, Honore S, Colson P, Chabriere E, La Scola B, Rolain JM, Brouqui P and Raoult D (2020). Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized. Int J Antimicrob Agents 20: 105949.
Graham RL, Donaldson EF and Baric RS (2013). A decade after SARS: strategies for controlling emerging coronaviruses. Nat Rev Microbiol 11(12): 836-48.
Hegyi A and Ziebuhr J (2002). Conservation of substrate specificities among coronavirus main proteases. J Gen Virol 83(Pt 3): 595-9.
Jin Z, Du X, Xu Y, Deng Y, Liu M, Zhao Y, et al. (2020). The crystal structure of 2019-nCoV main protease in complex with an inhibitor N3, Nature. 1-8
Kahn JS, McIntosh K (2005). History and recent advances in coronavirus discovery. Pediatr Infect Dis J 24(11): S223-7.
Kerwin SM (2010). ChemBioOffice Ultra 2010 Suite. J Am Chem Soc 132(7): 2466-2467.
Khan RJ, Jha RK, Amera GM, Jain M, Singh E, Pathak A, et al (2020). Targeting SARS-CoV-2: a systematic drug repurposing approach to identify promising inhibitors against 3C-like proteinase and 2'-O-ribose methyltransferase. J Biomol Struct Dyn 20: 1-14.
Kim S, Chen J, Cheng T, Gindulyte A, He J, He S, Li Q, Shoemaker BA, Thiessen PA, Yu B, Zaslavsky L, Zhang J and Bolton EE (2019). PubChem 2019 update: improved access to chemical data. Nucleic Acids Res 47(D1): D1102-d1109.
Kupferschmidt Kai and Cohen Jon (2020). WHO launches global megatrial of the four most promising coronavirus treatments https://www.sciencemag.org/news/2020/03/who-launches-global-megatrial-four-most-promising-coronavirus-treatments# Accessed 10 May 2020.
Lima de Oliveira MD (2020). Docking and Molecular Dynamics studies of Saquinavir in complex with protease of SARS-CoV-2. 1-12.
Michel F, Sanner (1999). Python: A Programming Language for Software Integration and Development. J Mol Graph Model 17: 57-61.
Mishra A, Pathak Y and Tripathi V (2020). Natural compounds as potential inhibitors of novel coronavirus (COVID-19) main protease: An in silico study, Preprint 1-16.
Paraskevis D, Kostaki EG, Magiorkinis G, Panayiotakopoulos G, Sourvinos G and Tsiodras S (2020). Full-genome evolutionary analysis of the novel corona virus (2019-nCoV) rejects the hypothesis of emergence as a result of a recent recombination event. Infect Genet Evol 79: 104212.
Paules CI, Marston HD and Fauci AS (2020). Coronavirus Infections: More than just the common cold. Jama 323(8): 707-708.
Peiris JS, Lai ST, Poon LL, Guan Y, Yam LY, Lim W, Nicholls J, Yee WK, Yan WW, Cheung MT, Cheng VC, Chan KH, Tsang DN, Yung RW, Ng TK and Yuen KY (2003). Coronavirus as a possible cause of severe acute respiratory syndrome. Lancet 361(9366):1319-1325.
Pillaiyar T, Manickam M, Namasivayam V, Hayashi Y, Jung SH (2016). An Overview of Severe Acute Respiratory Syndrome-Coronavirus (SARS-CoV) 3CL Protease Inhibitors: Peptidomimetics and Small Molecule Chemotherapy. J Med Chem 59(14): 6595-628.
Rodríguez-Morales AJ, MacGregor K, Kanagarajah S, Patel D and Schlagenhauf P (2020). Going global – Travel and the 2019 novel coronavirus. Travel Med Infect Dis 33: 101578.
Savarino A, Di Trani L, Donatelli I, Cauda R and Cassone A (2006). New insights into the antiviral effects of chloroquine. Lancet Infect Dis 6(2): 67-9.
Trott O and Olson AJ (2010). AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J Comput Chem 31(2): 455-461.
Wang M, Cao R, Zhang L, Yang X, Liu J, Xu M, Shi Z and Hu Z (2020). Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res 30(3): 269-271.
Wang M, Cao R, Zhang L, Yang X, Liu J, Xu M. Shi Z, Hu Z, Zhong W and Xiao G (2020). Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res 30(3): 269-271.
Weiss SR and Leibowitz JL (2011). Coronavirus pathogenesis. Advances in virus research 81: 85-164.
Wu F, Zhao S, Yu B, Chen Y-M, Wang W, Song Z-G, et al (2020). A new coronavirus associated with human respiratory disease in China. Nature 579(7798): 265-9.
Wu R, Wang L, Kuo H-CD, Shannar A, Peter R, Chou PJ, et al (2020). An Update on Current Therapeutic Drugs Treating COVID-19. Curr Pharmacol Rep 1-15.
Xu Z, Yao H, Shen J, Wu N, Xu Y, Lu X, et al. (2020). Nelfinavir Is Active Against SARS-CoV-2 in Vero E6 Cells. ChemRxiv Preprint 1-4.
Yang H, Yang M, Ding Y, Liu Y, Lou Z, Zhou Z, et al (2003). The crystal structures of severe acute respiratory syndrome virus main protease and its complex with an inhibitor. Proc Natl Acad Sci USA 100(23):13190-5.
Yao X, Ye F, Zhang M, Cui C, Huang B, Niu P, Liu X, Zhao L, Dong E, Song C, Zhan S, Lu R, Li H and Tan W Liu D (2020). In vitro Antiviral Activity and Projection of Optimized Dosing Design of Hydroxychloroquine for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Clin Infect Dis 237.
Zakaryan H, Arabyan E, Oo A and Zandi K (2017). Flavonoids: promising natural compounds against viral infections. Arch Virol 162(9): 2539-2551.
Zhou P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W, et al (2020). A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 579(7798): 270-3.
