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Reviews

Plant-Derived Natural Non-Nucleoside Analog Inhibitors (NNAIs) against RNA-Dependent RNA Polymerase Complex (nsp7/nsp8/nsp12) of SARS-CoV-2

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References

  • Baer CF. Does mutation rate depend on itself. PLoS Biol. 2008;6(2):e52. doi:10.1371/journal.pbio.0060052. PMID: 18303954; PMCID: PMC2253642.
  • Duffy S. Why are RNA virus mutation rates so damn high? PLoS Biol. 2018;16(8):e3000003. doi:10.1371/journal.pbio.3000003. PMID: 30102691; PMCID: PMC6107253.
  • Carrasco-Hernandez R, Jácome R, López Vidal Y, Ponce de León S. Are RNA viruses candidate agents for the next global pandemic? A review. Ilar J. 2017;58(3):343–58. doi:10.1093/ilar/ilx026. PMID: 28985316; PMCID: PMC7108571.
  • Giovanetti M, Benedetti F, Campisi G, Ciccozzi A, Fabris S, Ceccarelli G, Tambone V, Caruso A, Angeletti S, Zella D, et al. Evolution patterns of SARS-CoV-2: Snapshot on its genome variants. Biochem Biophys Res Commun. 2021;538:88–91. doi:10.1016/j.bbrc.2020.10.102. Epub 2020 Nov 6. PMID: 33199021; PMCID: PMC7836704.
  • Mahrosh HS, Mustafa G. An in silico approach to target RNA-dependent RNA polymerase of COVID-19 with naturally occurring phytochemicals. Environ Dev Sustain. 2021;3:1–14. doi:10.1007/s10668-021-01373-5.Epub ahead of print. PMID: 33841038; PMCID: PMC8018901.
  • Mahrosh HS, Tanveer M, Arif R, Mustafa G. Computer-aided prediction and identification of phytochemicals as potential drug candidates against MERS-CoV. BioMed Res Int. 2021;2021:1–7. doi:10.1155/2021/5578689.
  • Perales C, Domingo E. Antiviral strategies based on lethal mutagenesis and error threshold. Curr Top Microbiol Immunol. 2016;392:323–39. doi:10.1007/82_2015_459. PMID: 26294225.
  • Pruijssers AJ, Denison MR. Nucleoside analogues for the treatment of coronavirus infections. Curr Opin Virol. 2019;35:57–62. doi:10.1016/j.coviro.2019.04.002. Epub 2019 May 21. PMID: 31125806; PMCID: PMC7102703.
  • Callaway E. Fast-spreading COVID variant can elude immune responses. Nature. 2021;589(7843):500–1. doi:10.1038/d41586-021-00121-z. PMID: 33479534.
  • Korber B, Fischer WM, Gnanakaran S, Yoon H, Theiler J, Abfalterer W, Hengartner N, Giorgi EE, Bhattacharya T, Foley B, Sheffield COVID-19 Genomics Group, et al. Tracking changes in SARS-CoV-2 spike: Evidence that D614G increases infectivity of the COVID-19 Virus. Cell. 2020;182(4):812–27.e19. doi:10.1016/j.cell.2020.06.043. Epub 2020 Jul 3. PMID: 32697968; PMCID: PMC7332439.
  • Koyama T, Weeraratne D, Snowdon JL, Parida L. Emergence of drift variants that may affect COVID-19 vaccine development and antibody treatment. Pathogens. 2020;9(5):324. PMID: 32357545; PMCID: PMC7281497. doi:10.3390/pathogens9050324.
  • Acharya A, Pandey K, Thurman M, Klug E, Trivedi J, Sharma K, Lorson CL, Singh K, Byrareddy SN. Discovery and evaluation of entry inhibitors for SARS-CoV-2 and its emerging variants. J Virol. 2021;22:JVI0143721. Epub ahead of print. PMID: 34550770. doi:10.1128/JVI.01437-21.
  • Aleem A, Akbar Samad AB, Slenker AK. Emerging variants of SARS-CoV-2 and novel therapeutics against coronavirus (COVID-19). In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishinsg; 2021. PMID: 34033342.
  • Krumm ZA, Lloyd GM, Francis CP, Nasif LH, Mitchell DA, Golde TE, Giasson BI, Xia Y. Precision therapeutic targets for COVID-19. Virol J. 2021;18(1):66. PMID: 33781287; PMCID: PMC8006140. doi:10.1186/s12985-021-01526-y.
  • Jin YH, Min JS, Jeon S, Lee J, Kim S, Park T, Park D, Jang MS, Park CM, Song JH, Kim HR, et al. Lycorine, a non-nucleoside RNA dependent RNA polymerase inhibitor, as potential treatment for emerging coronavirus infections. Phytomedicine. 2021;86:153440. doi:10.1016/j.phymed.2020.153440. Epub 2020 Dec 16. PMID: 33376043; PMCID: PMC7738280.
  • Tian L, Qiang T, Liang C, Ren X, Jia M, Zhang J, Li J, Wan M, YuWen X, Li H, et al. RNA-dependent RNA polymerase (RdRp) inhibitors: The current landscape and repurposing for the COVID-19 pandemic. Eur J Med Chem. 2021;213:113201. doi:10.1016/j.ejmech.2021.113201. Epub 2021 Jan 21. PMID: 33524687; PMCID: PMC7826122.
  • Jiang Y, Yin W, Xu HE. RNA-dependent RNA polymerase: Structure, mechanism, and drug discovery for COVID-19. Biochem Biophys Res Commun. 2021;538:47–53. doi:10.1016/j.bbrc.2020.08.116. Epub 2020 Sep 4. PMID: 32943188; PMCID: PMC7473028.
  • Jácome R, Campillo-Balderas JA, Ponce de León S, Becerra A, Lazcano A. Sofosbuvir as a potential alternative to treat the SARS-CoV-2 epidemic. Sci Rep. 2020;10(1):9294. doi:10.1038/s41598-020-66440-9. PMID: 32518317; PMCID: PMC7283245.
  • Wang Y, Anirudhan V, Du R, Cui Q, Rong L. RNA-dependent RNA polymerase of SARS-CoV-2 as a therapeutic target. J Med Virol. 2021;93(1):300–10. doi:10.1002/jmv.26264. Epub 2020 Jul 19. PMID: 32633831.
  • Zhu W, Chen CZ, Gorshkov K, Xu M, Lo DC, Zheng W. RNA-dependent RNA polymerase as a target for COVID-19 drug discovery. SLAS Discov. 2020;25(10):1141–51. doi:10.1177/2472555220942123. Epub 2020 Jul 13. PMID: 32660307; PMCID: PMC7684788.
  • Chien M, Anderson TK, Jockusch S, Tao C, Li X, Kumar S, Russo JJ, Kirchdoerfer RN, Ju J. Nucleotide analogues as inhibitors of SARS-CoV-2 polymerase, a key drug target for COVID-19. J Proteome Res. 2020;19(11):4690–7. doi:10.1021/acs.jproteome.0c00392. Epub 2020 Aug 5. PMID: 32692185; PMCID: PMC7640960.
  • Martinez MA. Clinical trials of repurposed antivirals for SARS-CoV-2. Antimicrob Agents Chemother. 2020;64(9):e01101–20. PMID: 32631826; PMCID: PMC7449177. doi:10.1128/AAC.01101-20.
  • Gao Y, Yan L, Huang Y, Liu F, Zhao Y, Cao L, Wang T, Sun Q, Ming Z, Zhang L, Ge J, et al. Structure of the RNA-dependent RNA polymerase from COVID-19 virus. Science. 2020;368(6492):779–82. doi:10.1126/science.abb7498. Epub 2020 Apr 10. PMID: 32277040; PMCID: PMC7164392.
  • Hillen HS, Kokic G, Farnung L, Dienemann C, Tegunov D, Cramer P. Structure of replicating SARS-CoV-2 polymerase. Nature. 2020;584(7819):154–6. doi:10.1038/s41586-020-2368-8. Epub 2020 May 21. PMID: 32438371.
  • White KA, Enjuanes L, Berkhout B. RNA virus replication, transcription and recombination. RNA Biol. 2011;8(2):182–3. doi:10.4161/rna.8.2.15663. Epub 2011 Mar 1. PMID: 21593586; PMCID: PMC3127097.
  • Huang J, Song W, Huang H, Sun Q. Pharmacological therapeutics targeting RNA-dependent RNA polymerase, proteinase and spike protein: From mechanistic studies to clinical trials for COVID-19. JCM. 2020;9(4):1131. PMID: 32326602; PMCID: PMC7231166. doi:10.3390/jcm9041131.
  • Černý J, Černá Bolfíková B, Valdés JJ, Grubhoffer L, Růžek D. Evolution of tertiary structure of viral RNA dependent polymerases. PLoS One. 2014;9(5):e96070. doi:10.1371/journal.pone.0096070. PMID: 24816789; PMCID: PMC4015915.
  • Kirchdoerfer RN, Ward AB. Structure of the SARS-CoV nsp12 polymerase bound to nsp7 and nsp8 co-factors. Nat Commun. 2019;10(1):2342. doi:10.1038/s41467-019-10280-3. PMID: 31138817; PMCID: PMC6538669.
  • Subissi L, Posthuma CC, Collet A, Zevenhoven-Dobbe JC, Gorbalenya AE, Decroly E, Snijder EJ, Canard B, Imbert I. One severe acute respiratory syndrome coronavirus protein complex integrates processive RNA polymerase and exonuclease activities. Proc Natl Acad Sci U S A. 2014;111(37):E3900–9. doi:10.1073/pnas.1323705111. Epub 2014 Sep 2. PMID: 25197083; PMCID: PMC4169972.
  • Ma Y, Wu L, Shaw N, Gao Y, Wang J, Sun Y, Lou Z, Yan L, Zhang R, Rao Z. Structural basis and functional analysis of the SARS coronavirus nsp14-nsp10 complex. Proc Natl Acad Sci U S A. 2015;112(30):9436–41. doi:10.1073/pnas.1508686112. Epub 2015 Jul 9. PMID: 26159422; PMCID: PMC4522806.
  • Hao W, Wojdyla JA, Zhao R, Han R, Das R, Zlatev I, Manoharan M, Wang M, Cui S. Crystal structure of Middle East respiratory syndrome coronavirus helicase. PLoS Pathog. 2017;13(6):e1006474. doi:10.1371/journal.ppat.1006474. PMID: 28651017; PMCID: PMC5501694.
  • Shannon A, Le NT, Selisko B, Eydoux C, Alvarez K, Guillemot JC, Decroly E, Peersen O, Ferron F, Canard B. Remdesivir and SARS-CoV-2: Structural requirements at both nsp12 RdRp and nsp14 Exonuclease active-sites. Antiviral Res. 2020;178:104793. doi:10.1016/j.antiviral.2020.104793. Epub 2020 Apr 10. PMID: 32283108; PMCID: PMC7151495.
  • Barakat K, Ahmed M, Tabana Y, Ha M. A ‘deep dive’ into the SARS-Cov-2 polymerase assembly: identifying novel allosteric sites and analyzing the hydrogen bond networks and correlated dynamics. J Biomol Struct Dyn. 2021;26:1–21. Epub ahead of print. PMID: 34034620. doi:10.1080/07391102.2021.1930162.
  • Gordon CJ, Tchesnokov EP, Woolner E, Perry JK, Feng JY, Porter DP, Götte M. Remdesivir is a direct-acting antiviral that inhibits RNA-dependent RNA polymerase from severe acute respiratory syndrome coronavirus 2 with high potency. J Biol Chem. 2020;295(20):6785–97. doi:10.1074/jbc.RA120.013679. Epub 2020 Apr 13. PMID: 32284326; PMCID: PMC7242698.
  • Vicenti I, Zazzi M, Saladini F. SARS-CoV-2 RNA-dependent RNA polymerase as a therapeutic target for COVID-19. Expert Opin Ther Pat. 2021;31(4):325–37. doi:10.1080/13543776.2021.1880568. Epub 2021 Mar 3. PMID: 33475441; PMCID: PMC7938656.
  • Wang L, Astone M, Alam SK, Zhu ZPW, Frank DA, Burgess SM, Hoeppner LH. Suppressing STAT3 activity protects the endothelial barrier from VEGF-mediated vascular permeability. Dis Model Mech. 2021;14(11):dmm049029. doi:10.1242/dmm.049029. Epub 2021 Nov 11. PMID: 34542605; PMCID: PMC8592016.
  • Morse JS, Lalonde T, Xu S, Liu WR. Learning from the past: Possible urgent prevention and treatment options for severe acute respiratory infections caused by 2019-nCoV. Chembiochem. 2020;21(5):730–8. doi:10.1002/cbic.202000047. Epub 2020 Feb 25. PMID: 32022370; PMCID: PMC7162020.
  • Yin W, Mao C, Luan X, Shen DD, Shen Q, Su H, Wang X, Zhou F, Zhao W, Gao M, Chang S, et al. Structural basis for inhibition of the RNA-dependent RNA polymerase from SARS-CoV-2 by remdesivir. Science. 2020;368(6498):1499–504. doi:10.1126/science.abc1560. Epub 2020 May 1. PMID: 32358203; PMCID: PMC7199908.
  • Lehmann KC, Gulyaeva A, Zevenhoven-Dobbe JC, Janssen GM, Ruben M, Overkleeft HS, van Veelen PA, Samborskiy DV, Kravchenko AA, Leontovich AM, et al. Discovery of an essential nucleotidylating activity associated with a newly delineated conserved domain in the RNA polymerase-containing protein of all nidoviruses. Nucleic Acids Res. 2015;43(17):8416–34. doi:10.1093/nar/gkv838. Epub 2015 Aug 24. PMID: 26304538; PMCID: PMC4787807.
  • McDonald SM. RNA synthetic mechanisms employed by diverse families of RNA viruses. Wiley Interdiscip Rev Rna. 2013;4(4):351–67. doi:10.1002/wrna.1164. Epub 2013 Apr 18. PMID: 23606593; PMCID: PMC7169773.
  • Ferrer-Orta C, Ferrero D, Verdaguer N. RNA-dependent RNA polymerases of picornaviruses: From the structure to regulatory mechanisms. Viruses. 2015;7(8):4438–60. doi:10.3390/v7082829. PMID: 26258787; PMCID: PMC4576190.
  • Te Velthuis AJ. Common and unique features of viral RNA-dependent polymerases. Cell Mol Life Sci. 2014;71(22):4403–20. doi:10.1007/s00018-014-1695-z. Epub 2014 Aug 1. PMID: 25080879; PMCID: PMC4207942.
  • Garriga D, Ferrer-Orta C, Querol-Audí J, Oliva B, Verdaguer N. Role of motif B loop in allosteric regulation of RNA-dependent RNA polymerization activity. J Mol Biol. 2013;425(13):2279–87. doi:10.1016/j.jmb.2013.03.034. Epub 2013 Mar 28. PMID: 23542342.
  • Vázquez AL, Alonso JM, Parra F. Mutation analysis of the GDD sequence motif of a calicivirus RNA-dependent RNA polymerase. J Virol. 2000;74(8):3888–91. doi:10.1128/jvi.74.8.3888-3891.2000. PMID: 10729164; PMCID: PMC111898.
  • Wang Y, Xiao M, Chen J, Zhang W, Luo J, Bao K, Nie M, Chen J, Li B. Mutational analysis of the GDD sequence motif of classical swine fever virus RNA-dependent RNA polymerases. Virus Genes. 2007;34(1):63–5. doi:10.1007/s11262-006-0001-z. Epub 2006 Aug 18. PMID: 16917742.
  • Shu B, Gong P. Structural basis of viral RNA-dependent RNA polymerase catalysis and translocation. Proc Natl Acad Sci U S A. 2016;113(28):E4005–14. doi:10.1073/pnas.1602591113. Epub 2016 Jun 23. PMID: 27339134; PMCID: PMC4948327.
  • Venkataraman S, Prasad BVLS, Selvarajan R. RNA dependent RNA polymerases: Insights from structure, function and evolution. Viruses. 2018;10(2):76. PMID: 29439438; PMCID: PMC5850383. doi:10.3390/v10020076.
  • Gong P, Peersen OB. Structural basis for active site closure by the poliovirus RNA-dependent RNA polymerase. Proc Natl Acad Sci U S A. 2010;107(52):22505–10. doi:10.1073/pnas.1007626107. Epub 2010 Dec 10. PMID: 21148772; PMCID: PMC3012486.
  • Kao CC, Singh P, Ecker DJ. De novo initiation of viral RNA-dependent RNA synthesis. Virology. 2001;287(2):251–60. doi:10.1006/viro.2001.1039. PMID: 11531403.
  • van Dijk AA, Makeyev EV, Bamford DH. Initiation of viral RNA-dependent RNA polymerization. J Gen Virol. 2004;85(Pt 5):1077–93. doi:10.1099/vir.0.19731-0. PMID: 15105525.
  • Ogden KM, Ramanathan HN, Patton JT. Mutational analysis of residues involved in nucleotide and divalent cation stabilization in the rotavirus RNA-dependent RNA polymerase catalytic pocket. Virology. 2012;431(1–2):12–20. doi:10.1016/j.virol.2012.05.009. Epub 2012 Jun 2. PMID: 22664357; PMCID: PMC3378758.
  • Huchting J. Targeting viral genome synthesis as broad-spectrum approach against RNA virus infections. Antivir Chem Chemother. 2020;28:2040206620976786. doi:10.1177/2040206620976786. PMID: 33297724; PMCID: PMC7734526.
  • Geraghty RJ, Aliota MT, Bonnac LF. Broad-spectrum antiviral strategies and nucleoside analogues. Viruses. 2021;13(4):667. PMID: 33924302; PMCID: PMC8069527. doi:10.3390/v13040667.
  • Domingo E, Holland JJ. RNA virus mutations and fitness for survival. Annu Rev Microbiol. 1997;51:151–78. doi:10.1146/annurev.micro.51.1.151. PMID: 9343347.
  • Ji X, Li Z. Medicinal chemistry strategies toward host targeting antiviral agents. Med Res Rev. 2020;40(5):1519–57. doi:10.1002/med.21664. Epub 2020 Feb 14. PMID: 32060956; PMCID: PMC7228277.
  • Zumla A, Chan JF, Azhar EI, Hui DS, Yuen KY. Coronaviruses - drug discovery and therapeutic options. Nat Rev Drug Discov. 2016;15(5):327–47. doi:10.1038/nrd.2015.37. Epub 2016 Feb 12. PMID: 26868298; PMCID: PMC7097181.
  • Aftab SO, Ghouri MZ, Masood MU, Haider Z, Khan Z, Ahmad A, Munawar N. Analysis of SARS-CoV-2 RNA-dependent RNA polymerase as a potential therapeutic drug target using a computational approach. J Transl Med. 2020;18(1):275. doi:10.1186/s12967-020-02439-0. PMID: 32635935; PMCID: PMC7339606.
  • Ju J, Li X, Kumar S, Jockusch S, Chien M, Tao C, Morozova I, Kalachikov S, Kirchdoerfer RN, Russo JJ. Nucleotide analogues as inhibitors of SARS-CoV Polymerase. Pharmacol Res Perspect. 2020;8(6):e00674. doi:10.1002/prp2.674. PMID: 33124786; PMCID: PMC7596664.
  • Naidu AS. Redox Life (Bio-Rep Education Series). Yorba Linda, California: Bio-Rep Media; 2013. ISBN:978-0982445112.
  • Boehr DD, Nussinov R, Wright PE. The role of dynamic conformational ensembles in biomolecular recognition. Nat Chem Biol. 2009;5(11):789–96. doi:10.1038/nchembio.232. Erratum in: Nat Chem Biol. 2009 Dec;5(12):954. PMID: 19841628; PMCID: PMC2916928.
  • Ishikita H, Saito K. Proton transfer reactions and hydrogen-bond networks in protein environments. J R Soc Interface. 2014;11(91):20130518. doi:10.1098/rsif.2013.0518. PMID: 24284891; PMCID: PMC3869154.
  • Menéndez CA, Accordino SR, Gerbino DC, Appignanesi GA. Hydrogen bond dynamic propensity studies for protein binding and drug design. PLoS One. 2016;11(10):e0165767. doi:10.1371/journal.pone.0165767. PMID: 27792778; PMCID: PMC5085089.
  • Bhardwaj VK, Singh R, Sharma J, Rajendran V, Purohit R, Kumar S. Identification of bioactive molecules from tea plant as SARS-CoV-2 main protease inhibitors. J Biomol Struct Dyn. 2021a;39(10):3449–58. doi:10.1080/07391102.2020.1766572. Epub 2020 May 20. PMID: 32397940; PMCID: PMC7256349.
  • Selisko B, Papageorgiou N, Ferron F, Canard B. Structural and functional basis of the fidelity of nucleotide selection by Flavivirus RNA-dependent RNA polymerases. Viruses. 2018;10(2):59. PMID: 29385764; PMCID: PMC5850366. doi:10.3390/v10020059.
  • Oberg B. Rational design of polymerase inhibitors as antiviral drugs. Antiviral Res. 2006;71(2-3):90–5. doi:10.1016/j.antiviral.2006.05.012. Epub 2006 Jun 6. PMID: 16820225.
  • Sharma PL, Nurpeisov V, Hernandez-Santiago B, Beltran T, Schinazi RF. Nucleoside inhibitors of human immunodeficiency virus type 1 reverse transcriptase. Curr Top Med Chem. 2004;4(9):895–919. doi:10.2174/1568026043388484. PMID: 15134548.
  • Deval J. Antimicrobial strategies: inhibition of viral polymerases by 3’-hydroxyl nucleosides. Drugs. 2009;69(2):151–66. doi:10.2165/00003495-200969020-00002. PMID: 19228073.
  • Reynard O, Nguyen XN, Alazard-Dany N, Barateau V, Cimarelli A, Volchkov VE. Identification of a new Ribonucleoside inhibitor of Ebola virus replication. Viruses. 2015;7(12):6233–40. doi:10.3390/v7122934. Erratum in: Viruses. 2016;8(5). pii: E137. doi:10.3390/v8050137. PMID: 26633464; PMCID: PMC4690858.
  • Alanazi AS, James E, Mehellou Y. The ProTide Prodrug Technology: Where next? ACS Med Chem Lett. 2019;10(1):2–5. doi:10.1021/acsmedchemlett.8b00586. PMID: 30655934; PMCID: PMC6331162.
  • Kokic G, Hillen HS, Tegunov D, Dienemann C, Seitz F, Schmitzova J, Farnung L, Siewert A, Höbartner C, Cramer P. Mechanism of SARS-CoV-2 polymerase stalling by remdesivir. Nat Commun. 2021;12(1):279. doi:10.1038/s41467-020-20542-0. PMID: 33436624; PMCID: PMC7804290.
  • Elfiky AA. Ribavirin, Remdesivir, Sofosbuvir, Galidesivir, and Tenofovir against SARS-CoV-2 RNA dependent RNA polymerase (RdRp): A molecular docking study. Life Sci. 2020;253:117592. doi:10.1016/j.lfs.2020.117592. Epub 2020 Mar 25. Erratum in: Life Sci. 2020 Oct 1;258:118350. PMID: 32222463; PMCID: PMC7102646.
  • Bertolin AP, Weissmann F, Zeng J, Posse V, Milligan JC, Canal B, Ulferts R, Wu M, Drury LS, Howell M, et al. Identifying SARS-CoV-2 antiviral compounds by screening for small molecule inhibitors of nsp12/7/8 RNA-dependent RNA polymerase. Biochem J. 2021;478(13):2425–43. doi:10.1042/BCJ20210200. PMID: 34198323; PMCID: PMC8286815.
  • Smith EC, Blanc H, Surdel MC, Vignuzzi M, Denison MR. Coronaviruses lacking exoribonuclease activity are susceptible to lethal mutagenesis: evidence for proofreading and potential therapeutics. PLoS Pathog. 2013;9(8):e1003565. doi:10.1371/journal.ppat.1003565. Epub 2013 Aug 15. Erratum in: PLoS Pathog. 2014 Jul;10(7):e1004342. Surdel, Matthew C [added]. PMID: 23966862; PMCID: PMC3744431. [23966862]
  • Khater S, Kumar P, Dasgupta N, Das G, Ray S, Prakash A. Combining SARS-CoV-2 proofreading exonuclease and RNA-dependent RNA polymerase inhibitors as a strategy to combat COVID-19: A high-throughput in silico screening. Front Microbiol. 2021;12:647693. doi:10.3389/fmicb.2021.647693. PMID: 34354677; PMCID: PMC8329495.
  • Sofia MJ, Chang W, Furman PA, Mosley RT, Ross BS. Nucleoside, nucleotide, and non-nucleoside inhibitors of hepatitis C virus NS5B RNA-dependent RNA-polymerase. J Med Chem. 2012;55(6):2481–531. doi:10.1021/jm201384j. Epub 2012 Jan 23. Erratum in: J Med Chem. 2017 Apr 13;60(7):3219. PMID: 22185586.
  • Xu X, Liu Y, Weiss S, Arnold E, Sarafianos SG, Ding J. Molecular model of SARS coronavirus polymerase: implications for biochemical functions and drug design. Nucleic Acids Res. 2003;31(24):7117–30. doi:10.1093/nar/gkg916. PMID: 14654687; PMCID: PMC291860.
  • Beaulieu PL, Bousquet Y, Gauthier J, Gillard J, Marquis M, McKercher G, Pellerin C, Valois S, Kukolj G. Non-nucleoside benzimidazole-based allosteric inhibitors of the hepatitis C virus NS5B polymerase: inhibition of subgenomic hepatitis C virus RNA replicons in Huh-7 cells. J Med Chem. 2004;47(27):6884–92. doi:10.1021/jm040134d. PMID: 15615537.
  • Wang M, Ng KK, Cherney MM, Chan L, Yannopoulos CG, Bedard J, Morin N, Nguyen-Ba N, Alaoui-Ismaili MH, Bethell RC, James MN. Non-nucleoside analogue inhibitors bind to an allosteric site on HCV NS5B polymerase. Crystal structures and mechanism of inhibition. J Biol Chem. 2003;278(11):9489–95. doi:10.1074/jbc.M209397200. Epub 2002 Dec 30. PMID: 12509436.
  • Liu Y, Lim BH, Jiang WW, Flentge CA, Hutchinson DK, Madigan DL, Randolph JT, Wagner R, Maring CJ, Kati WM, et al. Identification of aryl dihydrouracil derivatives as palm initiation site inhibitors of HCV NS5B polymerase. Bioorg Med Chem Lett. 2012;22(11):3747–50. doi:10.1016/j.bmcl.2012.04.017. Epub 2012 Apr 10. PMID: 22542020.
  • Cheng CC, Shipps GW, Jr, Yang Z, Kawahata N, Lesburg CA, Duca JS, Bandouveres J, Bracken JD, Jiang CK, Agrawal S, et al. Inhibitors of hepatitis C virus polymerase: synthesis and characterization of novel 2-oxy-6-fluoro-N-((S)-1-hydroxy-3-phenylpropan-2-yl)-benzamides. Bioorg Med Chem Lett. 2010;20(7):2119–24. doi:10.1016/j.bmcl.2010.02.054. Epub 2010 Feb 18. PMID: 20219368.
  • Duffy S, Shackelton LA, Holmes EC. Rates of evolutionary change in viruses: patterns and determinants. Nat Rev Genet. 2008;9(4):267–76. doi:10.1038/nrg2323. Epub 2008 Mar 4. PMID: 18319742.
  • Hoffmann HH, Kunz A, Simon VA, Palese P, Shaw ML. Broad-spectrum antiviral that interferes with de novo pyrimidine biosynthesis. Proc Natl Acad Sci U S A. 2011;108(14):5777–82. doi:10.1073/pnas.1101143108. Epub 2011 Mar 21. PMID: 21436031; PMCID: PMC3078400.
  • Mahrosh HS, Mustafa G. The COVID-19 puzzle: a global nightmare. Environ Dev Sustain. 2021;23(9):12710–28. Epub ahead of print. PMID: 33551672; PMCID: PMC7847536. doi:10.1007/s10668-021-01224-3.
  • Mei M, Tan X. Current strategies of antiviral drug discovery for COVID-19. Front Mol Biosci. 2021;8:671263. doi:10.3389/fmolb.2021.671263. PMID: 34055887; PMCID: PMC8155633.
  • Newman DJ, Cragg GM. Natural products as sources of new drugs from 1981 to 2014. J Nat Prod. 2016;79(3):629–61. doi:10.1021/acs.jnatprod.5b01055. Epub 2016 Feb 7. PMID: 26852623.
  • Lalani S, Poh CL. Flavonoids as antiviral agents for Enterovirus A71 (EV-A71). Viruses. 2020;12(2):184. Erratum in: Viruses. 2020 Jun 30;12(7): PMID: 32041232; PMCID: PMC7077323. doi:10.3390/v12020184.
  • Chojnacka K, Witek-Krowiak A, Skrzypczak D, Mikula K, Młynarz P. Phytochemicals containing biologically active polyphenols as an effective agent against Covid-19-inducing coronavirus. J Funct Foods. 2020;73:104146. doi:10.1016/j.jff.2020.104146. Epub 2020 Jul 30. PMID: 32834835; PMCID: PMC7392194.
  • Wan S, Xiang Y, Fang W, Zheng Y, Li B, Hu Y, Lang C, Huang D, Sun Q, Xiong Y, et al. Clinical features and treatment of COVID-19 patients in northeast Chongqing. J Med Virol. 2020;92(7):797–806. doi:10.1002/jmv.25783. Epub 2020 Apr 1. PMID: 32198776; PMCID: PMC7228368.
  • Mani JS, Johnson JB, Steel JC, Broszczak DA, Neilsen PM, Walsh KB, Naiker M. Natural product-derived phytochemicals as potential agents against coronaviruses: A review. Virus Res. 2020;284:197989. doi:10.1016/j.virusres.2020.197989. Epub 2020 Apr 30. PMID: 32360300; PMCID: PMC7190535.
  • Wiedemar N, Hauser DA, Mäser P. 100 Years of Suramin. Antimicrob Agents Chemother. 2020;64(3):e01168–19. PMID: 31844000; PMCID: PMC7038244. doi:10.1128/AAC.01168-19.
  • Wu K, Chong RA, Yu Q, Bai J, Spratt DE, Ching K, Lee C, Miao H, Tappin I, Hurwitz J, et al. Suramin inhibits cullin-RING E3 ubiquitin ligases. Proc Natl Acad Sci U S A. 2016;113(14):E2011–8. doi:10.1073/pnas.1601089113. Epub 2016 Mar 21. PMID: 27001857; PMCID: PMC4833235.
  • Albulescu IC, White-Scholten L, Tas A, Hoornweg TE, Ferla S, Kovacikova K, Smit JM, Brancale A, Snijder EJ, van Hemert MJ. Suramin inhibits chikungunya virus replication by interacting with virions and blocking the early steps of infection. Viruses. 2020;12(3):314. PMID: 32191995; PMCID: PMC7150963. doi:10.3390/v12030314.
  • Salgado-Benvindo C, Thaler M, Tas A, Ogando NS, Bredenbeek PJ, Ninaber DK, Wang Y, Hiemstra PS, Snijder EJ, van Hemert MJ. Suramin inhibits SARS-CoV-2 infection in cell culture by interfering with early steps of the replication cycle. Antimicrob Agents Chemother. 2020;64(8):e00900–20. PMID: 32513797; PMCID: PMC7526844. doi:10.1128/AAC.00900-20.
  • Yin W, Luan X, Li Z, Zhou Z, Wang Q, Gao M, Wang X, Zhou F, Shi J, You E, et al. Structural basis for inhibition of the SARS-CoV-2 RNA polymerase by suramin. Nat Struct Mol Biol. 2021;28(3):319–25. doi:10.1038/s41594-021-00570-0. Epub 2021 Mar 5. PMID: 33674802.
  • Bijak M. Silybin, a major bioactive component of Milk Thistle (Silybum marianum L. Gaernt.)-Chemistry. Bioavailabil Metabol Mol. 2017;22(11):1942. PMID: 29125572; PMCID: PMC6150307. doi:10.3390/molecules22111942.
  • Bosch-Barrera J, Martin-Castillo B, Buxó M, Brunet J, Encinar JA, Menendez JA. Silibinin and SARS-CoV-2: Dual targeting of host cytokine storm and virus replication machinery for clinical management of COVID-19 patients. JCM. 2020;9(6):1770. PMID: 32517353; PMCID: PMC7356916. doi:10.3390/jcm9061770.
  • Gao H, Ward PA. STAT3 and suppressor of cytokine signaling 3: potential targets in lung inflammatory responses. Expert Opin Ther Targets. 2007;11(7):869–80. doi:10.1517/14728222.11.7.869. PMID: 17614756.
  • Matsuyama T, Kubli SP, Yoshinaga SK, Pfeffer K, Mak TW. An aberrant STAT pathway is central to COVID-19. Cell Death Differ. 2020;27(12):3209–25. doi:10.1038/s41418-020-00633-7. Epub 2020 Oct 9. PMID: 33037393; PMCID: PMC7545020.
  • Tyagi A, Agarwal C, Dwyer-Nield LD, Singh RP, Malkinson AM, Agarwal R. Silibinin modulates TNF-α and IFN-γ mediated signaling to regulate COX2 and iNOS expression in tumorigenic mouse lung epithelial LM2 cells. Mol Carcinog. 2012;51(10):832–42. doi:10.1002/mc.20851. Epub 2011 Aug 31. PMID: 21882257.
  • Verdura S, Cuyàs E, Llorach-Parés L, Pérez-Sánchez A, Micol V, Nonell-Canals A, Joven J, Valiente M, Sánchez-Martínez M, Bosch-Barrera J, et al. Silibinin is a direct inhibitor of STAT3. Food Chem Toxicol. 2018;116(Pt B):161–72. doi:10.1016/j.fct.2018.04.028. Epub 2018 Apr 14. PMID: 29660364.
  • Zhang B, Wang B, Cao S, Wang Y, Wu D. Silybin attenuates LPS-induced lung injury in mice by inhibiting NF-κB signaling and NLRP3 activation. Int J Mol Med. 2017;39(5):1111–8. doi:10.3892/ijmm.2017.2935. Epub 2017 Mar 27. PMID: 28350048; PMCID: PMC5403282.
  • Tian L, Li W, Wang T. Therapeutic effects of silibinin on LPS-induced acute lung injury by inhibiting NLRP3 and NF-κB signaling pathways. Microb Pathog. 2017;108:104–8. doi:10.1016/j.micpath.2017.05.011. Epub 2017 May 5. PMID: 28483599.
  • Moltó J, Valle M, Miranda C, Cedeño S, Negredo E, Clotet B. Effect of milk thistle on the pharmacokinetics of darunavir-ritonavir in HIV-infected patients. Antimicrob Agents Chemother. 2012;56(6):2837–41. doi:10.1128/AAC.00025-12. Epub 2012 Mar 19. PMID: 22430963; PMCID: PMC3370734.
  • Xu J, Xu Z, Zheng W. A review of the antiviral role of green tea catechins. Molecules. 2017;22(8):1337. PMID: 28805687; PMCID: PMC6152177. doi:10.3390/molecules22081337.
  • Bhardwaj VK, Singh R, Sharma J, Rajendran V, Purohit R, Kumar S. Bioactive molecules of tea as potential inhibitors for RNA-Dependent RNA Polymerase of SARS-CoV-2. Front Med (Lausanne). 2021b;8:684020. doi:10.3389/fmed.2021.684020. PMID: 34136511; PMCID: PMC8200525.
  • Du A, Zheng R, Disoma C, Li S, Chen Z, Li S, Liu P, Zhou Y, Shen Y, Liu S, et al. Epigallocatechin-3-gallate, an active ingredient of Traditional Chinese Medicines, inhibits the 3CLpro activity of SARS-CoV-2. Int J Biol Macromol. 2021;176:1–12. doi:10.1016/j.ijbiomac.2021.02.012. Epub 2021 Feb 4. PMID: 33548314; PMCID: PMC7859723.
  • Sharma J, Kumar Bhardwaj V, Singh R, Rajendran V, Purohit R, Kumar S. An in-silico evaluation of different bioactive molecules of tea for their inhibition potency against non structural protein-15 of SARS-CoV-2. Food Chem. 2021;346:128933. doi:10.1016/j.foodchem.2020.128933. Epub 2020 Dec 28. PMID: 33418408; PMCID: PMC7831997.
  • Chen CN, Lin CP, Huang KK, Chen WC, Hsieh HP, Liang PH, Hsu JT. Inhibition of SARS-CoV 3C-like protease activity by theaflavin-3,3’-digallate (TF3). Evid Based Complement Alternat Med. 2005;2(2):209–15. doi:10.1093/ecam/neh081. Epub 2005 Apr 7. PMID: 15937562; PMCID: PMC1142193.
  • Chowdhury P, Sahuc ME, Rouillé Y, Rivière C, Bonneau N, Vandeputte A, Brodin P, Goswami M, Bandyopadhyay T, Dubuisson J, et al. Theaflavins, polyphenols of black tea, inhibit entry of hepatitis C virus in cell culture. PLoS One. 2018;13(11):e0198226. PMID: 30485282; PMCID: PMC6261387. doi:10.1371/journal.pone.0198226.
  • Gogoi M, Borkotoky M, Borchetia S, Chowdhury P, Mahanta S, Barooah AK. Black tea bioactives as inhibitors of multiple targets of SARS-CoV-2 (3CLpro, PLpro and RdRp): a virtual screening and molecular dynamic simulation study. J Biomol Struct Dyn. 2021;10:1–24. Epub ahead of print. PMID: 33715595. doi:10.1080/07391102.2021.1897679.
  • Lung J, Lin YS, Yang YH, Chou YL, Shu LH, Cheng YC, Liu HT, Wu CY. The potential chemical structure of anti-SARS-CoV-2 RNA-dependent RNA polymerase. J Med Virol. 2020;92(6):693–7. doi:10.1002/jmv.25761. Epub 2020 Mar 18. Erratum in: J Med Virol. 2020 Oct;92(10):2248. PMID: 32167173; PMCID: PMC7228302.
  • Song J, Zhang L, Xu Y, Yang D, Zhang L, Yang S, Zhang W, Wang J, Tian S, Yang S, et al. The comprehensive study on the therapeutic effects of baicalein for the treatment of COVID-19 in vivo and in vitro. Biochem Pharmacol. 2021;183:114302. doi:10.1016/j.bcp.2020.114302. Epub 2020 Oct 27. PMID: 33121927; PMCID: PMC7588320.
  • Zandi K, Musall K, Oo A, Cao D, Liang B, Hassandarvish P, Lan S, Slack RL, Kirby KA, Bassit L, et al. Baicalein and baicalin inhibit SARS-CoV-2 RNA-dependent-RNA polymerase. Microorganisms. 2021;9(5):893. PMID: 33921971; PMCID: PMC8143456. doi:10.3390/microorganisms9050893.
  • Zhao Q, Chen XY, Martin C. Scutellaria baicalensis, the golden herb from the garden of Chinese medicinal plants. Sci Bull (Beijing). 2016;61(18):1391–8. doi:10.1007/s11434-016-1136-5. Epub 2016 Jul 8. PMID: 27730005; PMCID: PMC5031759.
  • Li Y, Song K, Zhang H, Yuan M, An N, Wei Y, Wang L, Sun Y, Xing Y, Gao Y. Anti-inflammatory and immunomodulatory effects of baicalin in cerebrovascular and neurological disorders. Brain Res Bull. 2020;164:314–24. doi:10.1016/j.brainresbull.2020.08.016. Epub 2020 Aug 26. PMID: 32858128.
  • Deschamps JD, Kenyon VA, Holman TR. Baicalein is a potent in vitro inhibitor against both reticulocyte 15-human and platelet 12-human lipoxygenases. Bioorg Med Chem. 2006;14(12):4295–301. doi:10.1016/j.bmc.2006.01.057. Epub 2006 Feb 24. PMID: 16500106.
  • Moghaddam E, Teoh BT, Sam SS, Lani R, Hassandarvish P, Chik Z, Yueh A, Abubakar S, Zandi K. Baicalin, a metabolite of baicalein with antiviral activity against dengue virus. Sci Rep. 2014;4:5452. doi:10.1038/srep05452. PMID: 24965553; PMCID: PMC4071309.
  • Oo A, Teoh BT, Sam SS, Bakar SA, Zandi K. Baicalein and baicalin as Zika virus inhibitors. Arch Virol. 2019;164(2):585–93. doi:10.1007/s00705-018-4083-4. Epub 2018 Nov 3. PMID: 30392049.
  • Nguyen HL, Thai NQ, Truong DT, Li MS. Remdesivir strongly binds to both RNA-dependent RNA polymerase and main protease of SARS-CoV-2: Evidence from molecular simulations. J Phys Chem B. 2020;124(50):11337–48. doi:10.1021/acs.jpcb.0c07312. Epub 2020 Dec 2. PMID: 33264025; PMCID: PMC7724981.
  • Satomi H, Umemura K, Ueno A, Hatano T, Okuda T, Noro T. Carbonic anhydrase inhibitors from the pericarps of Punica granatum L. Biol Pharm Bull. 1993;16(8):787–90. doi:10.1248/bpb.16.787. PMID: 8220326.
  • Li X, Deng Y, Zheng Z, Huang W, Chen L, Tong Q, Ming Y. Corilagin, a promising medicinal herbal agent. Biomed Pharmacother. 2018;99:43–50. doi:10.1016/j.biopha.2018.01.030. Epub 2018 Jan 8. PMID: 29324311.
  • Li Q, Yi D, Lei X, Zhao J, Zhang Y, Cui X, Xiao X, Jiao T, Dong X, Zhao X, et al. Corilagin inhibits SARS-CoV-2 replication by targeting viral RNA-dependent RNA polymerase. Acta Pharm Sin B. 2021b;11(6):1555–67. doi:10.1016/j.apsb.2021.02.011. Epub 2021 Feb 15. PMID: 33614402; PMCID: PMC7883726.
  • Mosquera-Yuqui F, Lopez-Guerra N, Moncayo-Palacio EA. Targeting the 3CLpro and RdRp of SARS-CoV-2 with phytochemicals from medicinal plants of the Andean Region: molecular docking and molecular dynamics simulations. J Biomol Struct Dyn. 2020;21:1–14. Epub ahead of print. PMID: 33084512; PMCID: PMC7657401. doi:10.1080/07391102.2020.1835716.
  • Man MQ, Yang B, Elias PM. Benefits of hesperidin for cutaneous functions. Evid Based Complement Alternat Med. 2019;2019:2676307. doi:10.1155/2019/2676307. PMID: 31061668; PMCID: PMC6466919.
  • Cao Z, Yang P, Zhou Q. Multiple biological functions and pharmacological effects of lycorine. Sci China Chem. 2013;56(10):1382–91. doi:10.1007/s11426-013-4967-9. Epub 2013 Aug 24. PMID: 32215001; PMCID: PMC7088923.
  • Li SY, Chen C, Zhang HQ, Guo HY, Wang H, Wang L, Zhang X, Hua SN, Yu J, Xiao PG, et al. Identification of natural compounds with antiviral activities against SARS-associated coronavirus. Antiviral Res. 2005;67(1):18–23. doi:10.1016/j.antiviral.2005.02.007. PMID: 15885816; PMCID: PMC7114104.
  • Shen L, Niu J, Wang C, Huang B, Wang W, Zhu N, Deng Y, Wang H, Ye F, Cen S, et al. High-throughput screening and identification of potent broad-spectrum inhibitors of coronaviruses. J Virol. 2019;93(12):e00023–19. PMID: 30918074; PMCID: PMC6613765. doi:10.1128/JVI.00023-19.
  • Jin Z, Wang H, Duan Y, Yang H. The main protease and RNA-dependent RNA polymerase are two prime targets for SARS-CoV-2. Biochem Biophys Res Commun. 2021;538:63–71. doi:10.1016/j.bbrc.2020.10.091. Epub 2020 Nov 21. PMID: 33288200; PMCID: PMC7680044.
  • Khan A, Khan M, Saleem S, Babar Z, Ali A, Khan AA, Sardar Z, Hamayun F, Ali SS, Wei DQ. Phylogenetic analysis and structural perspectives of RNA-dependent RNA-polymerase inhibition from SARs-CoV-2 with natural products. Interdiscip Sci. 2020;12(3):335–48. doi:10.1007/s12539-020-00381-9. Epub 2020 Jul 3. PMID: 32617855; PMCID: PMC7332347.
  • Chang YC, Hsieh PW, Chang FR, Wu RR, Liaw CC, Lee KH, Wu YC. Two new protopines argemexicaines A and B and the anti-HIV alkaloid 6-acetonyldihydrochelerythrine from formosan Argemone mexicana. Planta Med. 2003;69(2):148–52. doi:10.1055/s-2003-37710. PMID: 12624820.
  • Pandeya KB, Ganeshpurkar A, Mishra MK. Natural RNA dependent RNA polymerase inhibitors: Molecular docking studies of some biologically active alkaloids of Argemone mexicana. Med Hypotheses. 2020;144:109905. doi:10.1016/j.mehy.2020.109905. Epub 2020 Jun 1. PMID: 32535456; PMCID: PMC7262531.
  • Rosmalena R, Elya B, Dewi BE, Fithriyah F, Desti H, Angelina M, Hanafi M, Lotulung PD, Prasasty VD, Seto D. The antiviral effect of Indonesian medicinal plant extracts against Dengue virus in vitro and in silico. Pathogens. 2019;8(2):85. PMID: 31234495; PMCID: PMC6631455. doi:10.3390/pathogens8020085.
  • Gani MA, Nurhan AD, Maulana S, Siswodihardjo S, Shinta DW, Khotib J. Structure-based virtual screening of bioactive compounds from Indonesian medical plants against severe acute respiratory syndrome coronavirus-2. J Adv Pharm Technol Res. 2021;12(2):120–6. doi:10.4103/japtr.JAPTR_88_21. Epub 2021 Apr 27. PMID: 34159141; PMCID: PMC8177144.
  • Shaldam MA, Yahya G, Mohamed NH, Abdel-Daim MM. Al Naggar Y. In silico screening of potent bioactive compounds from honeybee products against COVID-19 target enzymes. Environ Sci Pollut Res Int. 2021;2:1–8. doi:10.1007/s11356-021-14195-9.Epub ahead of print. PMID: 33934306; PMCID: PMC8088405.
  • Strassmann G, D’Alessandro F, Fong M, Nordan RP, Nickel P, Chizzonite R. Suramin blocks the binding of interleukin-1 to its receptor and neutralizes IL-1 biological activities. Int J Immunopharmacol. 1994;16(11):931–9. PMID: 7868298. doi:10.1016/0192-0561(94)00054-9.
  • Choi YH, Yan GH. Silibinin attenuates mast cell-mediated anaphylaxis-like reactions. Biol Pharm Bull. 2009;32(5):868–75. doi:10.1248/bpb.32.868. PMID: 19420756.
  • Song YA, Park YL, Yoon SH, Kim KY, Cho SB, Lee WS, Chung IJ, Joo YE. Black tea polyphenol theaflavin suppresses LPS-induced ICAM-1 and VCAM-1 expression via blockage of NF-κB and JNK activation in intestinal epithelial cells. Inflamm Res. 2011;60(5):493–500. doi:10.1007/s00011-010-0296-z. Epub 2010 Dec 24. PMID: 21184129.
  • Kumar P, Maurya PK. Epigallocatechin-3-gallate protects erythrocyte Ca(2+)-ATPase and Na(+)/K(+)-ATPase against oxidative induced damage during aging in humans. Adv Pharm Bull. 2014;4(Suppl 1):443–7. doi:10.5681/apb.2014.065.Epub 2014 Aug 25. PMID: 25364660; PMCID: PMC4213783.
  • Zhao WZ, Wang HT, Huang HJ, Lo YL, Lin AM. Neuroprotective effects of baicalein on acrolein-induced neurotoxicity in the nigrostriatal dopaminergic system of rat brain. Mol Neurobiol. 2018;55(1):130–7. doi:10.1007/s12035-017-0725-x. PMID: 28866823.
  • Zhao L, Zhang SL, Tao JY, Pang R, Jin F, Guo YJ, Dong JH, Ye P, Zhao HY, Zheng GH. Preliminary exploration on anti-inflammatory mechanism of Corilagin (beta-1-O-galloyl-3,6-(R)-hexahydroxydiphenoyl-D-glucose) in vitro. Int Immunopharmacol. 2008;8(7):1059–64. doi:10.1016/j.intimp.2008.03.003. Epub 2008 Mar 31. PMID: 18486919.
  • Yamamoto M, Suzuki A, Jokura H, Yamamoto N, Hase T. Glucosyl hesperidin prevents endothelial dysfunction and oxidative stress in spontaneously hypertensive rats. Nutrition. 2008;24(5):470–6. doi:10.1016/j.nut.2008.01.010. Epub 2008 Mar 10. PMID: 18329851.
  • Ge X, Meng X, Fei D, Kang K, Wang Q, Zhao M. Lycorine attenuates lipopolysaccharide-induced acute lung injury through the HMGB1/TLRs/NF-κB pathway. 3 Biotech. 2020;10(8):369. doi:10.1007/s13205-020-02364-5. Epub 2020 Aug 1. PMID: 32818131; PMCID: PMC7395800.
  • Gu MY, Kim J, Yang HO. The neuroprotective effects of justicidin A on amyloid beta25-35-induced neuronal cell death through inhibition of Tau hyperphosphorylation and induction of autophagy in SH-SY5Y Cells. Neurochem Res. 2016;41(6):1458–67. doi:10.1007/s11064-016-1857-5. Epub 2016 Feb 18. PMID: 26887582.
  • Zheng J, Chan T, Zhu L, Yan X, Cao Z, Wang Y, Zhou F. The inhibitory effects of camptothecin (CPT) and its derivatives on the substrate uptakes mediated by human solute carrier transporters (SLCs). Xenobiotica. 2016;46(9):831–40. doi:10.3109/00498254.2015.1129080. Epub 2016 Jan 8. PMID: 26744836.
  • Simunkova M, Barbierikova Z, Jomova K, Hudecova L, Lauro P, Alwasel SH, Alhazza I, Rhodes CJ, Valko M. Antioxidant vs. Prooxidant properties of the flavonoid, kaempferol, in the presence of Cu(II) ions: A ROS-scavenging activity, Fenton reaction and DNA damage study. IJMS. 2021;22(4):1619. PMID: 33562744; PMCID: PMC7915082. doi:10.3390/ijms22041619.
  • Saleh J, Peyssonnaux C, Singh KK, Edeas M. Mitochondria and microbiota dysfunction in COVID-19 pathogenesis. Mitochondrion. 2020;54:1–7. doi:10.1016/j.mito.2020.06.008. Epub 2020 Jun 20. PMID: 32574708; PMCID: PMC7837003.
  • Li S, Ma F, Yokota T, Garcia G, Jr, Palermo A, Wang Y, Farrell C, Wang YC, Wu R, Zhou Z, Pan C, et al. Metabolic reprogramming and epigenetic changes of vital organs in SARS-CoV-2-induced systemic toxicity. JCI Insight. 2021c;6(2):e145027. PMID: 33284134; PMCID: PMC7934846. doi:10.1172/jci.insight.145027.
  • Moolamalla STR, Balasubramanian R, Chauhan R, Priyakumar UD, Vinod PK. Host metabolic reprogramming in response to SARS-CoV-2 infection: A systems biology approach. Microb Pathog. 2021;158:105114. doi:10.1016/j.micpath.2021.105114. Epub ahead of print. PMID: 34333072; PMCID: PMC8321700.
  • Patil R, Chikhale R, Khanal P, Gurav N, Ayyanar M, Sinha S, Prasad S, Dey YN, Wanjari M, Gurav SS. Computational and network pharmacology analysis of bioflavonoids as possible natural antiviral compounds in COVID-19. Inform Med Unlocked. 2021;22:100504. doi:10.1016/j.imu.2020.100504. Epub 2020 Dec 23. PMID: 33363251; PMCID: PMC7756171.
  • Harrison C. Coronavirus puts drug repurposing on the fast track. Nat Biotechnol. 2020;38(4):379–81. doi:10.1038/d41587-020-00003-1. PMID: 32205870.
  • Murgueitio MS, Bermudez M, Mortier J, Wolber G. In silico virtual screening approaches for anti-viral drug discovery. Drug Discov Today Technol. 2012;9(3):e219–e225. doi:10.1016/j.ddtec.2012.07.009. PMID: 24990575; PMCID: PMC7105918.
  • Aronskyy I, Masoudi-Sobhanzadeh Y, Cappuccio A, Zaslavsky E. Advances in the computational landscape for repurposed drugs against COVID-19. Drug Discov Today. 2021;30. S1359-6446(21):00335-4. doi:10.1016/j.drudis.2021.07.026. doi: Epub ahead of print. PMID: 34339864; PMCID: PMC8323501.
  • Li JG, Xu H. Chinese Medicine in fighting against Covid-19: Role and inspiration. Chin J Integr Med. 2021a;27(1):3–6. doi:10.1007/s11655-020-2860-x. Epub 2021 Jan 8. PMID: 33420601; PMCID: PMC7792556.

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