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Coronaviruses

Author(s): Chandan Sarkar, Sarmin Jamaddar, Milon Mondal, Abul Bashar Ripon Khalipha, Muhammad Torequl Islam* and Mohammad S. Mubarak*

DOI: 10.2174/2666796701999201116124851

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Natural Products as Anti-COVID-19 Agents: An In Silico Study

Article ID: e300421188012 Pages: 8

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Abstract

Background: The coronavirus disease 2019 (COVID-19) is a life-threatening viral infection caused by a positive-strand RNA virus belonging to the Coronaviridae family called severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2). This virus has infected millions of peoples and caused hundreds of thousands of deaths around the world. Unfortunately, to date, there is no specific cure for SARS-CoV-2 infection, although researchers are working tirelessly to come up with a drug against this virus. Recently, the main viral protease has been discovered and is regarded as an appropriate target for antiviral agents in the search for the treatment of SARS-CoV-2 infection due to its role in polyproteins processing coronavirus replication.

Materials and Methods: This investigation (an in silico study) explores the effectiveness of 16 natural compounds from a literature survey against the protease of SARS-CoV-2 in an attempt to identify a promising antiviral agent through a molecular docking study.

Results: Among the 16 compounds studied, apigenin, alpha-hederin, and asiatic acid exhibited significant docking performance and interacted with several amino acid residues of the main protease of SARS-CoV-2.

Conclusion: In summary, apigenin, alpha-hederin, and asiatic acid protease inhibitors may be effective potential antiviral agents against the main viral protease (Mpro) to combat SARS-CoV-2.

Keywords: SARS-CoV-2, COVID-19, protease inhibitors, natural products, in silico screening, apigenin.

Graphical Abstract

[1]
Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020; 395(10223): 497-506.
[http://dx.doi.org/10.1016/S0140-6736(20)30183-5] [PMID: 31986264]
[2]
Cui J, Li F, Shi ZL. Origin and evolution of pathogenic coronaviruses. Nat Rev Microbiol 2019; 17(3): 181-92.
[http://dx.doi.org/10.1038/s41579-018-0118-9] [PMID: 30531947]
[3]
Centers for Disease Control and Prevention. 2019 Novel Coronavirus (2019-nCoV) 2020. Available from: https://www.cdc.gov/coronavirus/2019-ncov/index.html
[4]
Dhama K, Pawaiya R, Chakraborty S, Tiwari RMS, Verma A. Coronavirus infection in equines: A review. Asian J Anim Vet Adv 2014; 9: 164-76.
[http://dx.doi.org/10.3923/ajava.2014.164.176]
[5]
Hegyi A, Friebe A, Gorbalenya AE, Ziebuhr J. Mutational analysis of the active centre of coronavirus 3C-like proteases. J Gen Virol 2002; 83(Pt 3): 581-93.
[http://dx.doi.org/10.1099/0022-1317-83-3-581] [PMID: 11842253]
[6]
UNICEF. COVID-19: What you should know and how to protect yourself. Available from: https://www.unicef.org/indonesia/novel-coronavirus-covid-19-outbreak-what-you-shouldknow
[7]
WHO. WHO weekly epidemiological update - 17 November 2020. Available from: https://www.who.int/publications/m/item/weekly-epidemiological-update---17-november-2020
[8]
Anand K, Ziebuhr J, Wadhwani P, Mesters JR, Hilgenfeld R. Coronavirus main proteinase (3CLpro) structure: basis for design of anti-SARS drugs. Science 2003; 300(5626): 1763-7.
[http://dx.doi.org/10.1126/science.1085658] [PMID: 12746549]
[9]
Joshi T, Joshi T, Sharma P, et al. In silico screening of natural compounds against COVID-19 by targeting Mpro and ACE2 using molecular docking. Eur Rev Med Pharmacol Sci 2020; 24(8): 4529-36.
[PMID: 32373991]
[10]
Ganjhu RK, Mudgal PP, Maity H, et al. Herbal plants and plant preparations as remedial approach for viral diseases. Virusdisease 2015; 26(4): 225-36.
[http://dx.doi.org/10.1007/s13337-015-0276-6] [PMID: 26645032]
[11]
Williamson EM, Liu X, Izzo AA. Trends in use, pharmacology, and clinical applications of emerging herbal nutraceuticals. Br J Pharmacol 2020; 177(6): 1227-40.
[http://dx.doi.org/10.1111/bph.14943] [PMID: 31799702]
[12]
Oyero OG, Toyama M, Mitsuhiro N, et al. Selective inhibition of hepatitis C virus replication by alpha-zam, a Nigella sativaseed formulation. Afr J Tradit Complement Altern Med 2016; 13(6): 144-8.
[http://dx.doi.org/10.21010/ajtcam.v13i6.20] [PMID: 28480371]
[13]
Moghadamtousi SZM, Nikzad S, Kadir HA, Abubakar S, Zandi K. Potential antiviral agents from marine fungi: An overview. Mar Drugs 2015; 13(7): 4520-38.
[http://dx.doi.org/10.3390/md13074520] [PMID: 26204947]
[14]
Oliveira AFCS, Teixeira RR, Oliveira AS, Souza AP, Silva ML, Paula SO. Potential antivirals: Natural products targeting replication enzymes of dengue and chikungunya viruses. Molecules 2017; 22(3): 505.
[http://dx.doi.org/10.3390/molecules22030505] [PMID: 28327521]
[15]
Wang SX, Zhang XS, Guan HS, Wang W. Potential anti-HPV and related cancer agents from marine resources: an overview. Mar Drugs 2014; 12(4): 2019-35.
[http://dx.doi.org/10.3390/md12042019] [PMID: 24705500]
[16]
Neumann H, Neumann-Staubitz P. Synthetic biology approaches in drug discovery and pharmaceutical biotechnology. Appl Microbiol Biotechnol 2010; 87(1): 75-86.
[http://dx.doi.org/10.1007/s00253-010-2578-3] [PMID: 20396881]
[17]
Denaro M, Smeriglio A, Barreca D, et al. Antiviral activity of plants and their isolated bioactive compounds: An update. Phytother Res 2020; 34(4): 742-68.
[http://dx.doi.org/10.1002/ptr.6575] [PMID: 31858645]
[18]
Liu X, Zhang B, Jin Z, Yang H, Rao Z. The crystal structure of 2019-nCoV mainprotease in complex with an inhibitor N3. PDB code 6LU7 2019. Available from: https://www.rcsb.org/structure/6lu7
[19]
Mishra A, Jain A, Arora N. Mapping B-cell epitopes of major and minor peanut allergens and identifying residues contributing to IgE binding. J Sci Food Agric 2016; 96(2): 539-47.
[http://dx.doi.org/10.1002/jsfa.7121] [PMID: 25652191]
[20]
Chan JFW, Yuan S, Kok KH, et al. A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster. Lancet 2020; 395(10223): 514-23.
[http://dx.doi.org/10.1016/S0140-6736(20)30154-9] [PMID: 31986261]
[21]
Fan K, Wei P, Feng Q, et al. Biosynthesis, purification, and substrate specificity of severe acute respiratory syndrome coronavirus 3C-like proteinase. J Biol Chem 2004; 279(3): 1637-42.
[http://dx.doi.org/10.1074/jbc.M310875200] [PMID: 14561748]
[22]
Fan K, Ma L, Han X, et al. The substrate specificity of SARS coronavirus 3C-like proteinase. Biochem Biophys Res Commun 2005; 329(3): 934-40.
[http://dx.doi.org/10.1016/j.bbrc.2005.02.061] [PMID: 15752746]
[23]
Berry M, Fielding BC, Gamieldien J. Potential broad spectrum inhibitors of the coronavirus 3CLpro: A virtual screening and structure-based drug design study. Viruses 2015; 7(12): 6642-60.
[http://dx.doi.org/10.3390/v7122963] [PMID: 26694449]
[24]
Dayer MR, Taleb-Gassabi S, Dayer MS. Lopinavir; A Potent drug against coronavirus infection: Insight from molecular docking study. Arch Clin Infect Dis 2017; 12(4)e13823
[http://dx.doi.org/10.5812/archcid.13823]
[25]
Prior AM, Kim Y, Weerasekara S, et al. Design, synthesis, and bioevaluation of viral 3C and 3C-like protease inhibitors. Bioorg Med Chem Lett 2013; 23(23): 6317-20.
[http://dx.doi.org/10.1016/j.bmcl.2013.09.070] [PMID: 24125888]
[26]
Jardim ACG, Shimizu JF, Rahal P, Harris M. Plant-derived antivirals against hepatitis C virus infection. Virol J 2018; 15(1): 34.
[http://dx.doi.org/10.1186/s12985-018-0945-3] [PMID: 29439720]
[27]
Islam MT, Sarkar C, El-Kersh DM, et al. Natural products and their derivatives against coronavirus: A review of the non-clinical and pre-clinical data. Phytother Res 2020.
[http://dx.doi.org/10.1002/ptr.6700] [PMID: 32248575]
[28]
Ryu YB, Jeong HJ, Kim JH, et al. Biflavonoids from Torreya nucifera displaying SARS-CoV 3CL(pro) inhibition. Bioorg Med Chem 2010; 18(22): 7940-7.
[http://dx.doi.org/10.1016/j.bmc.2010.09.035] [PMID: 20934345]
[29]
Lin CW, Tsai FJ, Tsai CH, et al. Anti-SARS coronavirus 3C-like protease effects of Isatis indigotica root and plant-derived phenolic compounds. Antiviral Res 2005; 68(1): 36-42.
[http://dx.doi.org/10.1016/j.antiviral.2005.07.002] [PMID: 16115693]
[30]
Wen CC, Kuo YH, Jan JT, et al. Specific plant terpenoids and lignoids possess potent antiviral activities against severe acute respiratory syndrome coronavirus. J Med Chem 2007; 50(17): 4087-95.
[http://dx.doi.org/10.1021/jm070295s] [PMID: 17663539]
[31]
Chen CN, Lin CP, Huang KK, et al. Inhibition of SARS-CoV 3C-like protease activity by theaflavin-3, 3′-digallate (TF3). Evid Based Complement Alternat Med 2005; 2(2): 209-15.
[http://dx.doi.org/10.1093/ecam/neh081] [PMID: 15937562]
[32]
Yu MS, Lee J, Lee JM, et al. Identification of myricetin and scutellarein as novel chemical inhibitors of the SARS coronavirus helicase, nsP13. Bioorg Med Chem Lett 2012; 22(12): 4049-54.
[http://dx.doi.org/10.1016/j.bmcl.2012.04.081] [PMID: 22578462]
[33]
Hakobyan A, Arabyan E, Avetisyan A, Abroyan L, Hakobyan L, Zakaryan H. Apigenin inhibits African swine fever virus infection in vitro. Arch Virol 2016; 161(12): 3445-53.
[http://dx.doi.org/10.1007/s00705-016-3061-y] [PMID: 27638776]
[34]
Hong EH, Song JH, Shim A, et al. Extract enabled mice to overcome insufficient protection against influenza A/PR/8 virus infection under suboptimal treatment with oseltamivir. PLoS One 2015; 10(6)e0131089
[http://dx.doi.org/10.1371/journal.pone.0131089] [PMID: 26098681]
[35]
Chen JY, Xu QW, Xu H, Huang ZH. Asiatic acid promotes p21 (WAF1/CIP1) protein stability through attenuation of NDR1/2 dependent phosphorylation of p21 (WAF1/CIP1) inHepG2 human hepatoma cells. Asian Pac J Cancer Prev 2014; 15(2): 963-7.
[36]
O’Rourke A, Kremb S, Duggan BM, et al. Identification of a 3-alkylpyridinium compound from the Red Sea sponge amphimedon chloros with in vitro inhibitory activity against the West Nile virusNS3 protease. Molecules 2018; 23(6): 1472.
[http://dx.doi.org/10.3390/molecules23061472] [PMID: 29912151]
[37]
Mounce BC, Cesaro T, Carrau L, Vallet T, Vignuzzi M. Curcumin inhibits Zika and chikungunya virus infection by inhibiting cell binding. Antiviral Res 2017; 142: 148-57.
[http://dx.doi.org/10.1016/j.antiviral.2017.03.014] [PMID: 28343845]
[38]
Barthelemy S, Vergnes L, Moynier M, Guyot D, Labidalle S, Bahraoui E. Curcumin and curcumin derivatives inhibit Tat-mediated transactivation of type 1 human immunodeficiency virus long terminal repeat. Res Virol 1998; 149(1): 43-52.
[http://dx.doi.org/10.1016/S0923-2516(97)86899-9] [PMID: 9561563]
[39]
Chen JX, Xue HJ, Ye WC, et al. Activity of andrographolide and its derivatives against influenza virus in vivo and in vitro. Biol Pharm Bull 2009; 32(8): 1385-91.
[http://dx.doi.org/10.1248/bpb.32.1385] [PMID: 19652378]