In silico study of various antiviral drugs, vitamins, and natural substances as potential binding compounds with SARS-CoV-2 main protease

Document Type: Original Article

Authors

1 Department of Horticulture, Al-Baath University, Homs, Syria

2 Department of Horticultural Sciences, UTCAN, University of Tehran, Iran

3 Department of Animal Science, Ferdowsi University of Mashhad, Mashhad, Iran

Abstract

The novel coronavirus (SARS-CoV-2) has without a doubt escalated to become a global crisis. Taking into consideration our limited knowledge regarding the virus, all the efforts to provide better understanding or explore the solutions are highly welcomed. In this article, 88 conventional drugs, 16 vitamins, and 63 natural (plant) compounds were chosen to perform a binding simulation with the reported COVID-19 main protease (Mpro) in search for probable inhibitors. Based on docking results, various vitamins (B9, A, K, and E vitamins) exhibited a significantly strong interaction with the studied receptor which might refer to the importance of these supplements in daily diets. Additionally, the strong ligand-protein interactions of some conventional drugs such as Pleconaril, Adefovir dipivoxil, and Stavudine in addition to plant-based compounds such as Curcumin (Curcuma longa), Anolignan A (Anogeissus acuminata), and Phyllamyricin B (Phyllanthus myrtifolius) render these compounds promising and recommended for further studies.

Keywords


  1. Guo YR, Cao QD, Hong ZS, Tan YY, Chen SD, Jin HJ, Tan KS, Wang DY, Yan Y. The origin, transmission and clinical therapies on coronavirus disease 2019 (COVID-19) outbreak–an update on the status. Mil. Med. Res. 2020;7(1):1-0. DOI
  2. Zhou P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W, Si HR, Zhu Y, Li B, Huang CL, Chen HD. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020;579(7798):270-3. DOI
  3. Li W, Shi Z, Yu M, Ren W, Smith C, Epstein JH, Wang H, Crameri G, Hu Z, Zhang H, Zhang J. Bats are natural reservoirs of SARS-like coronaviruses. Science. 2005;310(5748):676-9. DOI
  4. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395(10223):497–506. DOI
  5. Jin YH, Cai L, Cheng ZS, Cheng H, Deng T, Fan YP, Fang C, Huang D, Huang LQ, Huang Q, Han Y. A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version). Mil. Med. Res. 2020 Dec 1;7(1):4. DOI
  6. Lauer SA, Grantz KH, Bi Q, Jones FK, Zheng Q, Meredith HR, Azman AS, Reich NG, Lessler J. The incubation period of coronavirus disease 2019 (COVID-19) from publicly reported confirmed cases: estimation and application. Ann. Intern. Med. 2020 Mar 10. DOI
  7. who.int [Internet]. WHO Director-General's opening remarks at the media briefing on COVID-19 - 11 March 2020 [cited 2020 Mar 25]. Available from: Link
  8. Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, Erichsen S, Schiergens TS, Herrler G, Wu NH, Nitsche A, Müller MA. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell. 2020. DOI
  9. Adedeji AO, Severson W, Jonsson C, Singh K, Weiss SR, Sarafianos SG. Novel inhibitors of severe acute respiratory syndrome coronavirus entry that act by three distinct mechanisms. J. Virol. 2013;87(14):8017-28. DOI
  10. Zhou Y, Hou Y, Shen J, Huang Y, Martin W, Cheng F. Network-based drug repurposing for novel coronavirus 2019-nCoV/SARS-CoV-2. Cell Discov. 2020;6(1):1-8. DOI
  11. Xue X, Yu H, Yang H, Xue F, Wu Z, Shen W, Li J, Zhou Z, Ding Y, Zhao Q, Zhang XC. Structures of two coronavirus main proteases: implications for substrate binding and antiviral drug design. J. Virol. 2008;82(5):2515-27. DOI
  12. Jin, Z., Du, X., Xu, Y. et al. Structure of Mpro from COVID-19 virus and discovery of its inhibitors. Nature (2020). DOI
  13. Gao J, Tian Z, Yang X. Breakthrough: Chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies. Biosci. Trends. 2020. DOI
  14. Touret F, de Lamballerie X. Of chloroquine and COVID-19. Antivir. Res. 2020:104762. DOI
  15. Wang M, Cao R, Zhang L, Yang X, Liu J, Xu M, Shi Z, Hu Z, Zhong W, Xiao G. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res. 2020;30(3):269-71. DOI
  16. Gautret P, Lagier JC, Parola P, Meddeb L, Mailhe M, Doudier B, Courjon J, Giordanengo V, Vieira VE, Dupont HT, Honoré S. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. Int. J. Antimicrob. Agents. 2020:105949. DOI
  17. Chan KW, Wong VT, Tang SC. COVID-19: An Update on the Epidemiological, Clinical, Preventive and Therapeutic Evidence and Guidelines of Integrative Chinese–Western Medicine for the Management of 2019 Novel Coronavirus Disease. Am. J. Chin. Med. 2020:1-26. DOI
  18. Heck CI, De Mejia EG. Yerba Mate Tea (Ilex paraguariensis): a comprehensive review on chemistry, health implications, and technological considerations. J. Food Sci. 2007;72(9):R138-51. DOI
  19. Cos P, Maes L, Vanden Berghe D, Hermans N, Pieters L, Vlietinck A. Plant substances as anti-HIV agents selected according to their putative mechanism of action. J. Nat. Prod. 2004;67(2):284-93. DOI
  20. Allahverdiyev AM, Bagirova M, Yaman S, Koc RC, Abamor ES, Ates SC, Baydar SY, Elcicek S, Oztel ON. Development of new antiherpetic drugs based on plant compounds. InFighting Multidrug Resistance with Herbal Extracts, Essential Oils and Their Components 2013:245-59. Academic Press. DOI
  21. Thomsen R, Christensen MH. MolDock: a new technique for high-accuracy molecular docking. J. Med. Chem. 2006;49(11):3315-21. DOI
  22. Wong SE, Lightstone FC. Accounting for water molecules in drug design. Expert opinion on drug discovery. 2011;6(1):65-74.
  23. Wikipedia contributors. List of antiviral drugs [Internet]. Wikipedia, The Free Encyclopedia; 2020 Mar 20, 06:47 UTC [cited 2020 Mar 25]. Available from: Link
  24. Patra JK, Das G, Bose S, Banerjee S, Vishnuprasad CN, del Pilar Rodriguez‐Torres M, Shin HS. Star anise (Illicium verum): Chemical compounds, antiviral properties, and clinical relevance. Phytother. Res. 2020. DOI
  25. Kurapati KR, Atluri VS, Samikkannu T, Garcia G, Nair MP. Natural products as anti-HIV agents and role in HIV-associated neurocognitive disorders (HAND): a brief overview. Front. Microbiol. 2016;6:1444. DOI
  26. Soleymani S, Zabihollahi R, Shahbazi S, Bolhassani A. Antiviral effects of saffron and its major ingredients. Curr. Drug Deliv. 2018;15(5):698-704. DOI
  27. Sax PE, Wohl D, Yin MT, Post F, DeJesus E, Saag M, Pozniak A, Thompson M, Podzamczer D, Molina JM, Oka S. Tenofovir alafenamide versus tenofovir disoproxil fumarate, coformulated with elvitegravir, cobicistat, and emtricitabine, for initial treatment of HIV-1 infection: two randomised, double-blind, phase 3, non-inferiority trials. Lancet. 2015;385(9987):2606-15. DOI
  28. Wikipedia contributors. Tenofovir alafenamide [Internet]. Wikipedia, The Free Encyclopedia; 2020 Mar 26, 05:58 UTC [cited 2020 Apr 2]. Available from: Link
  29. Marcellin P, Chang TT, Lim SG, Tong MJ, Sievert W, Shiffman ML, Jeffers L, Goodman Z, Wulfsohn MS, Xiong S, Fry J. Adefovir dipivoxil for the treatment of hepatitis B e antigen–positive chronic hepatitis B. N. Engl. J. Med. 2003;348(9):808-16. DOI
  30. Manolakopoulos S, Bethanis S, Koutsounas S, Goulis J, Vlachogiannakos J, Christias E, Saveriadis A, Pavlidis C, Triantos C, Christidou A, Papatheodoridis G. Long‐term therapy with adefovir dipivoxil in hepatitis B e antigen‐negative patients developing resistance to lamivudine. Alimentary pharmacology & therapeutics. 2008;27(3):266-73. DOI
  31. ADHOC International Steering Committee. A randomized placebo‐controlled trial of adefovir dipivoxil in advanced HIV infection: the ADHOC trial. HIV Med. 2002;3(4):229-38. DOI
  32. Qaqish RB, Mattes KA, Ritchie DJ. Adefovir dipivoxil: a new antiviral agent for the treatment of hepatitis B virus infection. Clin. Ther. 2003;25(12):3084-99. DOI
  33. Noble S, Goa KL. Amprenavir. Drugs. 2000;60(6):1383-410. DOI
  34. Steigbigel RT, Cooper DA, Kumar PN, Eron JE, Schechter M, Markowitz M, Loutfy MR, Lennox JL, Gatell JM, Rockstroh JK, Katlama C. Raltegravir with optimized background therapy for resistant HIV-1 infection. N. Engl. J. Med. 2008;359(4):339-54.
  35. Eraikhuemen N, Thornton AM, Branch III E, Huynh ST, Farley C. Combating non-nucleoside reverse transcriptase inhibitor resistance with a focus on etravirine (Intelence) for HIV-1 infection. Pharm. Ther. 2008;33(8):445.
  36. Martin DF, Kuppermann BD, Wolitz RA, Palestine AG, Li H, Robinson CA, Roche Ganciclovir Study Group. Oral ganciclovir for patients with cytomegalovirus retinitis treated with a ganciclovir implant. N. Engl. J. Med. 1999;340(14):1063-70. DOI
  37. Hayden FG, Coats T, Kim K, Hassman HA, Blatter MM, Zhang B, Liu S. Oral pleconaril treatment of picornavirus-associated viral respiratory illness in adults: efficacy and tolerability in phase II clinical trials. Antivir. Ther. 2002;7(1):53-66.
  38. Kawamura K, Hayakawa J, Akahoshi Y, Harada N, Nakano H, Kameda K, Ugai T, Wada H, Yamasaki R, Ishihara Y, Sakamoto K. Low-dose acyclovir prophylaxis for the prevention of herpes simplex virus and varicella zoster virus diseases after autologous hematopoietic stem cell transplantation. Int. J. Hematol. 2015;102(2):230-7. DOI
  39. Colombier MA, Molina JM. Doravirine: a review. Curr Opin HIV AIDS. 2018;13(4):308-14. DOI
  40. Jackson A, McGowan I. Long-acting rilpivirine for HIV prevention. Curr Opin HIV AIDS. 2015;10(4):253-7. DOI
  41. Kimberlin DW, Jester PM, Sánchez PJ, Ahmed A, Arav-Boger R, Michaels MG, Ashouri N, Englund JA, Estrada B, Jacobs RF, Romero JR. Valganciclovir for symptomatic congenital cytomegalovirus disease. N. Engl. J. Med. 2015;372(10):933-43. DOI
  42. Vermehren J, Park JS, Jacobson IM, Zeuzem S. Challenges and perspectives of direct antivirals for the treatment of hepatitis C virus infection. Int. J. Hepatol. 2018;69(5):1178-87. DOI
  43. Nayak D, Boxi A, Ashe S, Thathapudi NC, Nayak B. Stavudine loaded gelatin liposomes for HIV therapy: Preparation, characterization and in vitro cytotoxic evaluation. Mater. Sci. Eng. C. 2017;73:406-16. DOI
  44. Li H, Wang YM, Xu JY, Cao B. Potential antiviral therapeutics for 2019 Novel Coronavirus. Chinese journal of tuberculosis and respiratory diseases. 2020;43:E002-. DOI
  45. Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, Wang B, Xiang H, Cheng Z, Xiong Y, Zhao Y. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus–infected pneumonia in Wuhan, China. Jama. 2020. DOI
  46. Rothan HA, Byrareddy SN. The epidemiology and pathogenesis of coronavirus disease (COVID-19) outbreak. J. Autoimmun. 2020:102433. DOI
  47. Min BS, Miyashiro H, Hattori M. Inhibitory effects of quinones on RNase H activity associated with HIV‐1 reverse transcriptase. Phytother. Res. 2002;16(S1):57-62. DOI
  48. Wang LS, Wang YR, Ye DW, Liu QQ. A review of the 2019 Novel Coronavirus (COVID-19) based on current evidence. Int. J. Antimicrob. Agents. 2020:105948. DOI
  49. Nonnecke BJ, McGill JL, Ridpath JF, Sacco RE, Lippolis JD, Reinhardt TA. Acute phase response elicited by experimental bovine diarrhea virus (BVDV) infection is associated with decreased vitamin D and E status of vitamin-replete preruminant calves. Journal of dairy science. 2014;97(9):5566-79. DOI
  50. Sui Z, Salto R, Li J, Craik C, de Montellano PR. Inhibition of the HIV-1 and HIV-2 proteases by curcumin and curcumin boron complexes. Bioorg. Med. Chem. 1993;1(6):415-22. DOI
  51. Singh S, Aggarwal BB. Activation of transcription factor NF-κB is suppressed by curcumin (diferuloylmethane). J. Biol. Chem. 1995;270(42):24995-5000. DOI
  52. Natarajan K, Singh S, Burke TR, Grunberger D, Aggarwal BB. Caffeic acid phenethyl ester is a potent and specific inhibitor of activation of nuclear transcription factor NF-kappa B. Proc. Natl. Acad. Sci. U.S.A. 1996;93(17):9090-5. DOI
  53. Liu JS, Li L. Schisantherins P and Q, two lignans from Kadsura coccinea. Phytochemistry. 1995;38(4):1009-11. DOI
  54. Rimando AM, Pezzuto JM, Farnsworth NR, Santisuk T, Reutrakul V, Kawanishi K. New lignans from Anogeissus acuminata with HIV-1 reverse transcriptase inhibitory activity. J. Nat. Prod. 1994;57(7):896-904. DOI
  55. Wen CC, Kuo YH, Jan JT, Liang PH, Wang SY, Liu HG, Lee CK, Chang ST, Kuo CJ, Lee SS, Hou CC. Specific plant terpenoids and lignoids possess potent antiviral activities against severe acute respiratory syndrome coronavirus. J. Med. Chem. 2007;50(17):4087-95. DOI
  56. Arthur DE, Uzairu A. Molecular docking studies on the interaction of NCI anticancer analogues with human Phosphatidylinositol 4, 5-bisphosphate 3-kinase catalytic subunit. J. King Saud Univ. Sci. 2019;31(4):1151-66. DOI
  57. Zhou P, Zou J, Tian F, Shang Z. Fluorine Bonding — How Does It Work In Protein− Ligand Interactions?. J Chem Inf Model. 2009;49(10):2344-55. DOI

Articles in Press, Accepted Manuscript
Available Online from 01 July 2020
  • Receive Date: 08 April 2020
  • Revise Date: 16 April 2020
  • Accept Date: 16 April 2020