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Baicalein and baicalin as Zika virus inhibitors

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At present, there is no effective antiviral agent for Zika virus (ZIKV), an arbovirus that is known for its teratogenic effects on newborns. Baicalein and baicalin were found to be capable of downregulating ZIKV replication up to 10 hours postinfection, while prophylactic effects were evident in pre-treated cells. Baicalein exhibited its highest potency during intracellular ZIKV replication, whereas baicalin was most effective against virus entry. Our in silico interaction assays predicted that both compounds exhibited the strongest binding affinities towards ZIKV NS5, while the virus envelope glycoprotein was the least likely target protein. These findings serve as a crucial platform for further in-depth studies to decipher the underlying anti-ZIKV mechanism(s) of each compound.

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  1. Baud D, Gubler DJ, Schaub B, Lanteri MC, Musso D (2017) An update on Zika virus infection. The Lancet 390:2099–2109

  2. Heukelbach J, Alencar CH, Kelvin AA, de Oliveira WK, de Góes Cavalcanti LP (2016) Zika virus outbreak in Brazil. J Infect Dev Ctries 10(02):116–120

    Article  PubMed  Google Scholar 

  3. Méndez N, Oviedo-Pastrana M, Mattar S, Caicedo-Castro I, Arrieta G (2017) Zika virus disease, microcephaly and Guillain-Barré syndrome in Colombia: epidemiological situation during 21 months of the Zika virus outbreak, 2015–2017. Arch Public Health 75(1):65

    Article  PubMed  PubMed Central  Google Scholar 

  4. Chang C, Ortiz K, Ansari A, Gershwin ME (2016) The Zika outbreak of the 21st century. J Autoimmun 68:1–13

    Article  PubMed  Google Scholar 

  5. Holtzman M, Golden WC, Sheffield JS (2018) Zika virus infection in the pregnant woman. Clin Obstet Gynecol 61(1):177–185

    PubMed  Google Scholar 

  6. de Souza AS, de Oliveira-Szjenfeld PS, de Oliveira Melo AS, de Souza LAM, Batista AGM, Tovar-Moll F (2018) Imaging findings in congenital Zika virus infection syndrome: an update. Child Nerv Syst 34(1):85–93

    Article  Google Scholar 

  7. Gaudry A, Bos S, Viranaicken W, Roche M, Krejbich-Trotot P, Gadea G, Desprès P, El-Kalamouni C (2018) The flavonoid isoquercitrin precludes initiation of Zika virus infection in human cells. Int J Mol Sci 19(4):1093

    Article  CAS  PubMed Central  Google Scholar 

  8. Mounce BC, Cesaro T, Carrau L, Vallet T, Vignuzzi M (2017) Curcumin inhibits Zika and chikungunya virus infection by inhibiting cell binding. Antivir Res 142:148–157

    Article  CAS  PubMed  Google Scholar 

  9. Carneiro BM, Batista MN, Braga ACS, Nogueira ML, Rahal P (2016) The green tea molecule EGCG inhibits Zika virus entry. Virology 496:215–218

    Article  CAS  PubMed  Google Scholar 

  10. Zandi K, Teoh B-T, Sam S-S, Wong P-F, Mustafa MR, AbuBakar S (2012) Novel antiviral activity of baicalein against dengue virus. BMC Complement Altern Med 12(1):214

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Moghaddam E, Teoh B-T, Sam S-S, Lani R, Hassandarvish P, Chik Z, Yueh A, Abubakar S, Zandi K (2014) Baicalin, a metabolite of baicalein with antiviral activity against dengue virus. Sci Rep 4:5452

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Oo A, Rausalu K, Merits A, Higgs S, Vanlandingham D, Bakar SA, Zandi K (2018) Deciphering the potential of baicalin as an antiviral agent for Chikungunya virus infection. Antivir Res 150:101–111

    Article  CAS  PubMed  Google Scholar 

  13. Jin J, Chen Y, Wang D, Ma L, Guo M, Zhou C, Dou J (2018) The inhibitory effect of sodium baicalin on oseltamivir-resistant influenza A virus via reduction of neuraminidase activity. Arch Pharm Res 41(6):664–676

    Article  CAS  PubMed  Google Scholar 

  14. Oo A, Hassandarvish P, Chin SP, Lee VS, Bakar SA, Zandi K (2016) In silico study on anti-Chikungunya virus activity of hesperetin. PeerJ 4:e2602

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Hassandarvish P, Rothan HA, Rezaei S, Yusof R, Abubakar S, Zandi K (2016) In silico study on baicalein and baicalin as inhibitors of dengue virus replication. RSC Adv 6(37):31235–31247

    Article  CAS  Google Scholar 

  16. Bullard-Feibelman KM, Govero J, Zhu Z, Salazar V, Veselinovic M, Diamond MS, Geiss BJ (2017) The FDA-approved drug sofosbuvir inhibits Zika virus infection. Antivir Res 137:134–140

    Article  CAS  PubMed  Google Scholar 

  17. Chan JF-W, Chik KK-H, Yuan S, Yip CC-Y, Zhu Z, Tee K-M, Tsang JO-L, Chan CC-S, Poon VK-M, Lu G (2017) Novel antiviral activity and mechanism of bromocriptine as a Zika virus NS2B-NS3 protease inhibitor. Antivir Res 141:29–37

    Article  CAS  PubMed  Google Scholar 

  18. Johari J, Kianmehr A, Mustafa MR, Abubakar S, Zandi K (2012) Antiviral activity of baicalein and quercetin against the Japanese encephalitis virus. Int J Mol Sci 13(12):16785–16795

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Li BQ, Fu T, Dongyan Y, Mikovits JA, Ruscetti FW, Wang JM (2000) Flavonoid baicalin inhibits HIV-1 infection at the level of viral entry. Biochem Biophys Res Commun 276(2):534–538

    Article  CAS  PubMed  Google Scholar 

  20. Cheng F, da Silva SR, Huang I-C, Jung JU, Gao S-J (2018) Suppression of Zika virus infection and replication in endothelial cells and astrocytes by PKA inhibitor PKI 14-22. J Virol 92(4):e02019–02017

    Google Scholar 

  21. Fink SL, Vojtech L, Wagoner J, Slivinski NS, Jackson KJ, Wang R, Khadka S, Luthra P, Basler CF, Polyak SJ (2018) The antiviral drug arbidol inhibits Zika virus. Sci Rep 8(1):8989

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Wang B, Thurmond S, Hai R, Song J (2018) Structure and function of Zika virus NS5 protein: perspectives for drug design. Cell Mol Life Sci 75(10):1723–1736

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Sacramento CQ, De Melo GR, De Freitas CS, Rocha N, Hoelz LVB, Miranda M, Fintelman-Rodrigues N, Marttorelli A, Ferreira AC, Barbosa-Lima G (2017) The clinically approved antiviral drug sofosbuvir inhibits Zika virus replication. Sci Rep 7:40920

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Goo L, DeMaso CR, Pelc RS, Ledgerwood JE, Graham BS, Kuhn RJ, Pierson TC (2018) The Zika virus envelope protein glycan loop regulates virion antigenicity. Virology 515:191–202

    Article  CAS  PubMed  Google Scholar 

  25. Persaud M, Martinez-Lopez A, Buffone C, Porcelli SA, Diaz-Griffero F (2018) Infection by Zika viruses requires the transmembrane protein AXL, endocytosis and low pH. Virology 518:301–312

    Article  CAS  PubMed  Google Scholar 

  26. Meertens L, Labeau A, Dejarnac O, Cipriani S, Sinigaglia L, Bonnet-Madin L, Le Charpentier T, Hafirassou ML, Zamborlini A, Cao-Lormeau V-M (2017) Axl mediates ZIKA virus entry in human glial cells and modulates innate immune responses. Cell Rep 18(2):324–333

    Article  CAS  PubMed  Google Scholar 

  27. Chu M, Xu L, Zhang M-b, Chu Z-y, Wang Y-d (2015) Role of Baicalin in anti-influenza virus A as a potent inducer of IFN-gamma. BioMed research international 2015

  28. Li M, Shi A, Pang H, Xue W, Li Y, Cao G, Yan B, Dong F, Li K, Xiao W (2014) Safety, tolerability, and pharmacokinetics of a single ascending dose of baicalein chewable tablets in healthy subjects. J Ethnopharmacol 156:210–215

    Article  CAS  PubMed  Google Scholar 

  29. Fangueiro JF, Calpena AC, Clares B, Andreani T, Egea MA, Veiga FJ, Garcia ML, Silva AM, Souto EB (2016) Biopharmaceutical evaluation of epigallocatechin gallate-loaded cationic lipid nanoparticles (EGCG-LNs): in vivo, in vitro and ex vivo studies. Int J Pharm 502(1–2):161–169

    Article  CAS  PubMed  Google Scholar 

  30. Pechenov S, Bhattacharjee H, Yin D, Mittal S, Subramony JA (2017) Improving drug-like properties of insulin and GLP-1 via molecule design and formulation and improving diabetes management with device & drug delivery. Adv Drug Deliv Rev 112:106–122

    Article  CAS  PubMed  Google Scholar 

  31. Liu J, Lv S-S, Fu Z-Y, Hou L-L (2018) Baicalein enhances migration and invasion of extravillous trophoblasts via activation of the NF-κB pathway. Med Sci Monit 24:2983

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Wang G, Liang J, L-r Gao, Z-p Si, X-t Zhang, Liang G, Yan Y, Li K, Cheng X, Bao Y (2018) Baicalin administration attenuates hyperglycemia-induced malformation of cardiovascular system. Cell Death Dis 9(2):234

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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This work was funded by the University of Malaya via a Postgraduate Research Grant (PPP) (PG151-2016A).

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Correspondence to Keivan Zandi.

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The authors declare that they have no conflict of interest.

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This study does not involve any human participants or animals in any of its experimental procedures.

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Handling Editor: Tatjana Avsic-Zupanc.

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Oo, A., Teoh, B.T., Sam, S.S. et al. Baicalein and baicalin as Zika virus inhibitors. Arch Virol 164, 585–593 (2019).

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