Insight into the Natural Biomolecules (BMs): Promising Candidates as
Zika Virus Inhibitors

Kiran      Dobhal; Ruchika      Garg; Alka      Singh; Amit      Semwal
doi:10.2174/0118715265272414231226092146
Abstract

Zika virus (ZIKV) is among the relatively new infectious disease threats that include SARS-CoV-2, coronavirus, monkeypox (Mpox) virus, etc. ZIKV has been reported to cause severe health risks to the fetus. To date, satisfactory treatment is still not available for the treatment of ZIKV infection. This review examines the last five years of work using natural biomolecules (BMs) to counteract the ZIKV through virtual screening and in vitro investigations. Virtual screening has identified doramectin, pinocembrin, hesperidins, epigallocatechin gallate, pedalitin, and quercetin as potentially active versus ZIKV infection. In vitro, testing has shown that nordihydroguaiaretic acid, mefloquine, isoquercitrin, glycyrrhetinic acid, patentiflorin-A, rottlerin, and harringtonine can reduce ZIKV infections in cell lines. However, in vivo, testing is limited, fortunately, emetine, rottlerin, patentiflorin-A, and lycorine have shown in vivo anti- ZIKV potential. This review focuses on natural biomolecules that show a particularly high selective index (>10). There is limited in vivo and clinical trial data for natural BMs, which needs to be an active area of investigation. This review aims to compile the known reference data and discuss the barriers associated with discovering and using natural BM agents to control ZIKV infection.
Keywords: ZIKV, Biomolecules, Virtual, in-vitro, IC₅₀, virtual screening
Graphical Abstract

[1]
Pant P, Pandey S, Dall’Acqua S. The influence of environmental conditions on secondary metabolites in medicinal plants: A literature review. Chem Biodivers  2021; 18(11): e2100345.
 [http://dx.doi.org/10.1002/cbdv.202100345 ] [PMID:  34533273]

[2]
Kasote DM, Katyare SS, Hegde MV, Bae H. Significance of antioxidant potential of plants and its relevance to therapeutic applications. Int J Biol Sci  2015; 11(8): 982-91.
 [http://dx.doi.org/10.7150/ijbs.12096] [PMID:  26157352]

[3]
Lawson ADG, MacCoss M, Heer JP. Importance of rigidity in designing small molecule drugs to tackle protein–protein interactions (PPIs) through stabilization of desired conformers. J Med Chem  2018; 61(10): 4283-9.
 [http://dx.doi.org/10.1021/acs.jmedchem.7b01120 ] [PMID:  29140691]

[4]
Azab A, Nassar A, Azab A. Anti-inflammatory activity of natural products. Molecules  2016; 21(10): 1321.
 [http://dx.doi.org/10.3390/molecules21101321] [PMID:  27706084]

[5]
Debnath B, Singh WS, Das M, et al. Role of plant alkaloids on human health: A review of biological activities. Mater Today Chem  2018; 9: 56-72.
 [http://dx.doi.org/10.1016/j.mtchem.2018.05.001]

[6]
Jin J, Qiu S, Wang P, et al. Cardamonin inhibits breast cancer growth by repressing HIF-1α-dependent metabolic reprogramming. J Exp Clin Cancer Res  2019; 38(1): 377.
 [http://dx.doi.org/10.1186/s13046-019-1351-4]

[7]
Feng A, Yang S, Sun Y, Zhang L, Bo F, Li L. Development and evaluation of oleanolic acid dosage forms and its derivatives. Biomed Res Int  2020; 2020: 1308749.
 [http://dx.doi.org/10.1155/2020/1308749]

[8]
Ludwiczuk A, Skalicka-Woźniak K, Georgiev MI. Terpenoids. In: Pharmacognosy Fundamentals, Applications and Strategies.   2017; pp. 233-66.
 [http://dx.doi.org/10.1016/B978-0-12-802104-0.00011-1]

[9]
van de Velde ME, Kaspers GL, Abbink FCH, Wilhelm AJ, Ket JCF, van den Berg MH. Vincristine-induced peripheral neuropathy in children with cancer: A systematic review. Crit Rev Oncol Hematol  2017; 114: 114-30.
 [http://dx.doi.org/10.1016/j.critrevonc.2017.04.004 ] [PMID:  28477739]

[10]
Rahman AT. In silico study of the potential of endemic sumatra wild turmeric rhizomes (Curcuma Sumatrana: Zingiberaceae) as anti-cancer. Pharmacogn J  2022; 14: 6.

[11]
Garg R. Covid-19: A challenge towards the sustainability of health in platform era. J Pharm Negat Results  2022; 1666-78.

[12]
Dobhal K, Ghildiyal P, Ansori ANM, Jakhmola V. An international outburst of new form of monkeypox virus. J Pure Appl Microbiol  2022; 16(S1): 3013-24.
 [http://dx.doi.org/10.22207/JPAM.16.SPL1.01]

[13]
Tompa DR, Immanuel A, Srikanth S, Kadhirvel S. Trends and strategies to combat viral infections: A review on FDA approved antiviral drugs. Int J Biol Macromol  2021; 172: 524-41.
 [http://dx.doi.org/10.1016/j.ijbiomac.2021.01.076] [PMID:  33454328]

[14]
Plourde AR, Bloch EM. A literature review of zika virus. Emerg Infect Dis  2016; 22(7): 1185-92.
 [http://dx.doi.org/10.3201/eid2207.151990] [PMID:  27070380]

[15]
Lu AY, Gustin A, Newhouse D, Gale M Jr. Viral protein accumulation of zika virus variants links with regulation of innate immunity for differential control of viral replication, spread, and response to interferon. J Virol  2023; 97(5): e01982-22.
 [http://dx.doi.org/10.1128/jvi.01982-22] [PMID:  37162358]

[16]
Fong YD, Chu JJH. Natural products as Zika antivirals. Med Res Rev  2022; 42(5): 1739-80.
 [http://dx.doi.org/10.1002/med.21891] [PMID:  35593443]

[17]
Pandey SC, Pande V, Sati D, Upreti S, Samant M. Vaccination strategies to combat novel corona virus SARS-CoV-2. Life Sci  2020; 256: 117956.
 [http://dx.doi.org/10.1016/j.lfs.2020.117956] [PMID:  32535078]

[18]
Kumar APN, Kumar M, et al. Major phytochemicals: Recent advances in health benefits and extraction method. Molecules  2023; 28(2): 887.
 [http://dx.doi.org/10.3390/molecules28020887] [PMID:  36677944]

[19]
Dassanayake MK, Khoo TJ, Chong CH, Di Martino P. Molecular docking and in-silico analysis of natural biomolecules against dengue, ebola, zika, SARS-CoV-2 variants of concern and monkeypox virus. Int J Mol Sci  2022; 23(19): 11131.
 [http://dx.doi.org/10.3390/ijms231911131] [PMID:  36232431]

[20]
Yeasmin M, Molla MMA, Masud HMAA, Saif-Ur-Rahman KM. Safety and immunogenicity of Zika virus vaccine: A systematic review of clinical trials. Rev Med Virol  2023; 33(1): e2385.
 [http://dx.doi.org/10.1002/rmv.2385] [PMID:  35986594]

[21]
Katzelnick LC, Bos S, Harris E. Protective and enhancing interactions among dengue viruses 1-4 and Zika virus. Curr Opin Virol  2020; 43: 59-70.
 [http://dx.doi.org/10.1016/j.coviro.2020.08.006] [PMID:  32979816]

[22]
Poland GA, Ovsyannikova IG, Kennedy RB. Zika vaccine development: Current status. Vaccines  2019; 10: 1816.
 [http://dx.doi.org/10.1016/j.mayocp.2019.05.016]

[23]
Santiago HC, Pereira-Neto TA, Gonçalves-Pereira MH, Terzian ACB, Durbin AP. Peculiarities of zika immunity and vaccine development: Lessons from dengue and the contribution from controlled human infection model. Pathogens  2022; 11(3): 294.
 [http://dx.doi.org/10.3390/pathogens11030294] [PMID:  35335618]

[24]
Garg R, Piplani M, Singh Y, Joshi Y. Epidemiology, pathophysiology, and pharmacological status of asthma. Curr Respir Med Rev  2022; 18(4): 247-58.
 [http://dx.doi.org/10.2174/1573398X18666220526164329]

[25]
Javed F, Manzoor KN, Ali M, et al. Zika virus: What we need to know? J Basic Microbiol  2018; 58(1): 3-16.
 [http://dx.doi.org/10.1002/jobm.201700398] [PMID:  29131357]

[26]
Puerta-Guardo H, Glasner DR, Espinosa DA, et al. Flavivirus NS1 triggers tissue-specific vascular endothelial dysfunction reflecting disease tropism. Cell Rep  2019; 26(6): 1598-613.
 [http://dx.doi.org/10.1016/j.celrep.2019.01.036]

[27]
Zhang X, Xie X, Zou J, et al. Genetic and biochemical characterizations of Zika virus NS2A protein. Emerg Microbes Infect  2019; 8(1): 585-602.
 [http://dx.doi.org/10.1080/22221751.2019.1598291 ] [PMID:  30958095]

[28]
Xu S, Ci Y, Wang L, et al. Zika virus NS3 is a canonical RNA helicase stimulated by NS5 RNA polymerase. Nucleic Acids Res  2019; 47(16): 8693-707.
 [http://dx.doi.org/10.1093/nar/gkz650] [PMID:  31361901]

[29]
Hasan SS, Sevvana M, Kuhn RJ, Rossmann MG. Structural biology of Zika virus and other flaviviruses. Nat Struct Mol Biol  2018; 25(1): 13-20.
 [http://dx.doi.org/10.1038/s41594-017-0010-8] [PMID:  29323278]

[30]
Bisia M, Montenegro-Quinoñez CA, Dambach P, et al. Secondary vectors of Zika Virus, a systematic review of laboratory vector competence studies. PLoS Negl Trop Dis  2023; 17(8): e0011591.
 [http://dx.doi.org/10.1371/journal.pntd.0011591] [PMID:  37651473]

[31]
White MK, Wollebo HS, David Beckham J, Tyler KL, Khalili K. Zika virus: An emergent neuropathological agent. Ann Neurol  2016; 80(4): 479-89.
 [http://dx.doi.org/10.1002/ana.24748] [PMID:  27464346]

[32]
Zika Virus Countries. 2023. Available from: https://worldpopulationreview.com/country-rankings/zika-countries

[33]
Rastogi M, Sharma N, Singh SK. Flavivirus NS1: A multifaceted enigmatic viral protein. Virol J  2016; 13(1): 131.
 [http://dx.doi.org/10.1186/s12985-016-0590-7] [PMID:  27473856]

[34]
CDC. Zika travel information  2016.cdc.gov/zika/index.html

[35]
Buathong R. Lack of association between adverse pregnancy outcomes and zika antibodies among pregnant women in Thailand between 1997 and 2015. 2018. Available from: https://www.fondation-merieux.org/wp-content/uploads/2018/01/arboviruses-2018-rome-buathong.pdf

[36]
Bhardwaj U, Pandey N, Rastogi M, Singh SK. Gist of Zika Virus pathogenesis. Virology  2021; 560: 86-95.
 [http://dx.doi.org/10.1016/j.virol.2021.04.008] [PMID:  34051478]

[37]
Gutiérrez-Bugallo G, Piedra LA, Rodriguez M, et al. Vector-borne transmission and evolution of Zika virus. Nat Ecol Evol  2019; 3(4): 561-9.
 [http://dx.doi.org/10.1038/s41559-019-0836-z] [PMID:  30886369]

[38]
WHO. Guideline: Infant Feeding in Areas of Zika Virus Transmission.  2016. Available from: http://apps.who.int/iris/bitstream/10665/208875/1/9789 241549660_eng.pdf?ua=1

[39]
Agarwal A, Chaurasia D. The expanding arms of Zika virus: An updated review with recent Indian outbreaks. Rev Med Virol  2021; 31(1): 1-9.
 [http://dx.doi.org/10.1002/rmv.2145] [PMID:  33216418]

[40]
Khaiboullina SF, Ribeiro FM, Uppal T, Martynova EV, Rizvanov AA, Verma SC. Zika virus transmission through blood tissue barriers. Front Microbiol  2019; 10: 1465.
 [http://dx.doi.org/10.3389/fmicb.2019.01465]

[41]
Ayloo S, Gu C. Transcytosis at the blood–brain barrier. Curr Opin Neurobiol  2019; 57: 32-8.
 [http://dx.doi.org/10.1016/j.conb.2018.12.014] [PMID:  30708291]

[42]
Arvidsson M, Collet F, Hedström P. The Trojan-horse mechanism: How networks reduce gender segregation. Sci Adv  2021; 7(16): eabf6730.
 [http://dx.doi.org/10.1126/sciadv.abf6730] [PMID:  33863731]

[43]
Spadoni I, Fornasa G, Rescigno M. Organ-specific protection mediated by cooperation between vascular and epithelial barriers. Nat Rev Immunol  2017; 17(12): 761-73.
 [http://dx.doi.org/10.1038/nri.2017.100] [PMID:  28869253]

[44]
Todorovski T, Mendonça DA, Fernandes-Siqueira LO, et al. Targeting zika virus with new brain- and placenta-crossing peptide–porphyrin conjugates. Pharmaceutics  2022; 14(4): 738.
 [http://dx.doi.org/10.3390/pharmaceutics14040738] [PMID:  35456572]

[45]
Peregrine J, Gurung S, Lindgren MC, et al. Zika virus infection, reproductive organ targeting, and semen transmission in the male olive baboon. J Virol  2019; 94(1): e01434-e014319.
 [http://dx.doi.org/10.1128/JVI.01434-19]

[46]
Sheridan MA, Zhao X, Fernando RC, et al. Characterization of primary models of human trophoblast. Development  2021; 148(21): dev199749.
 [http://dx.doi.org/10.1242/dev.199749] [PMID:  34651188]

[47]
Komarasamy TV, Adnan NAA, James W, Balasubramaniam VRMT. Zika virus neuropathogenesis: The different brain cells, host factors and mechanisms involved. Front Immunol  2022; 13: 773191.
 [http://dx.doi.org/10.3389/fimmu.2022.773191] [PMID:  35371036]

[48]
Giraldo MI, Xia H, Aguilera-Aguirre L, et al. Envelope protein ubiquitination drives entry and pathogenesis of Zika virus. Nature  2020; 585(7825): 414-9.
 [http://dx.doi.org/10.1038/s41586-020-2457-8] [PMID:  32641828]

[49]
Borges-Vélez G, Arroyo JA, Cantres-Rosario YM, et al. Decreased CSTB, RAGE, and Axl receptor are associated with zika infection in the human placenta. Cells  2022; 11(22): 3627.
 [http://dx.doi.org/10.3390/cells11223627] [PMID:  36429055]

[50]
Pielnaa P, Al-Saadawe M, Saro A, et al. Zika virus-spread, epidemiology, genome, transmission cycle, clinical manifestation, associated challenges, vaccine and antiviral drug development. Virology  2020; 543: 34-42.
 [http://dx.doi.org/10.1016/j.virol.2020.01.015] [PMID:  32056845]

[51]
Bernardo-Menezes LC, Agrelli A, Oliveira ASLE, Moura RR, Crovella S, Brandão LAC. An overview of Zika virus genotypes and their infectivity. Rev Soc Bras Med Trop  2022; 55: e0263-2022.
 [http://dx.doi.org/10.1590/0037-8682-0263-2022] [PMID:  36197380]

[52]
Li XD, Deng CL, Yuan ZM, Ye HQ, Zhang B. Different degrees of 5'-to-3' DAR interactions modulate zika virus genome cyclization and host-specific replication. J Virol  2020; 94(5): e01602-19.
 [http://dx.doi.org/10.1128/JVI.01602-19]

[53]
Agrelli A, de Moura RR, Crovella S, Brandão LAC. ZIKA virus entry mechanisms in human cells. Infect Genet Evol  2019; 69: 22-9.
 [http://dx.doi.org/10.1016/j.meegid.2019.01.018] [PMID:  30658214]

[54]
Routhu NK, Lehoux SD, Rouse EA, et al. Glycosylation of zika virus is important in host–virus interaction and pathogenic potential. Int J Mol Sci  2019; 20(20): 5206.
 [http://dx.doi.org/10.3390/ijms20205206] [PMID:  31640124]

[55]
Bos S, Poirier-Beaudouin B, Seffer V, et al. Zika virus inhibits IFN-α response by human plasmacytoid dendritic cells and induces NS1-dependent triggering of CD303 (BDCA-2) signaling. Front Immunol  2020; 11: 582061.
 [http://dx.doi.org/10.3389/fimmu.2020.582061] [PMID:  33193389]

[56]
Wood KM, Smith CJ. Clathrin: The molecular shape shifter. Biochem J  2021; 478(16): 3099-123.
 [http://dx.doi.org/10.1042/BCJ20200740] [PMID:  34436540]

[57]
Persaud M, Martinez-Lopez A, Buffone C, Porcelli SA, Diaz-Griffero F. Infection by Zika viruses requires the transmembrane protein AXL, endocytosis and low pH. Virology  2018; 518: 301-12.
 [http://dx.doi.org/10.1016/j.virol.2018.03.009] [PMID:  29574335]

[58]
Xu MM, Wu B, Huang GG, et al. Hemin protects against Zika virus infection by disrupting virus-endosome fusion. Antiviral Res  2022; 203: 105347.
 [http://dx.doi.org/10.1016/j.antiviral.2022.105347] [PMID:  35643150]

[59]
Hackett BA, Cherry S. Flavivirus internalization is regulated by a size-dependent endocytic pathway. Proc Natl Acad Sci  2018; 115(16): 4246-51.
 [http://dx.doi.org/10.1073/pnas.1720032115] [PMID:  29610346]

[60]
Christian KM, Song H, Ming G. Pathophysiology and mechanisms of zika virus infection in the nervous system. Annu Rev Neurosci  2019; 42(1): 249-69.
 [http://dx.doi.org/10.1146/annurev-neuro-080317-062231] [PMID:  31283901]

[61]
Wagner RS. Cortical visual impairment in congenital zika syndrome. J Pediatr Ophthalmol Strabismus  2021; 58(2): 72.
 [http://dx.doi.org/10.3928/01913913-20210204-01 ] [PMID:  34038273]

[62]
Faizan MI, Abdullah M, Ali S, Naqvi IH, Ahmed A, Parveen S. Zika virus-induced microcephaly and its possible molecular mechanism. Intervirology  2016; 59(3): 152-8.
 [http://dx.doi.org/10.1159/000452950] [PMID:  28081529]

[63]
Bernatchez JA, Tran LT, Li J, Luan Y, Siqueira-Neto JL, Li R. Drugs for the treatment of zika virus infection. J Med Chem  2020; 63(2): 470-89.
 [http://dx.doi.org/10.1021/acs.jmedchem.9b00775] [PMID:  31549836]

[64]
Marbán-Castro E, Goncé A, Fumadó V, Romero-Acevedo L, Bardají A. Zika virus infection in pregnant women and their children: A review. Eur J Obstet Gynecol Reprod Biol  2021; 265: 162-8.
 [http://dx.doi.org/10.1016/j.ejogrb.2021.07.012] [PMID:  34508989]

[65]
Xu Y, He Y, Momben-Abolfath S, et al. Entry and disposition of zika virus immune complexes in a tissue culture model of the maternal-fetal interface. Vaccines  2021; 9(2): 145.
 [http://dx.doi.org/10.3390/vaccines9020145] [PMID:  33670199]

[66]
Laureti M, Narayanan D, Rodriguez-Andres J, Fazakerley JK, Kedzierski L. Flavivirus receptors: Diversity, identity, and cell entry. Front Immunol  2018; 9: 2180.
 [http://dx.doi.org/10.3389/fimmu.2018.02180] [PMID:  30319635]

[67]
Freitas DA, Souza-Santos R, Carvalho LMA, et al. Congenital Zika syndrome: A systematic review. PLoS One  2020; 15(12): e0242367.
 [http://dx.doi.org/10.1371/journal.pone.0242367] [PMID:  33320867]

[68]
Espino A, Gouilly J, Chen Q, et al. The mechanisms underlying the immune control of Zika virus infection at the maternal-fetal interface. Front Immunol  2022; 13: 1000861.
 [http://dx.doi.org/10.3389/fimmu.2022.1000861] [PMID:  36483552]

[69]
Castanha PMS, Marques ETA. A glimmer of hope: Recent updates and future challenges in zika vaccine development. Viruses  2020; 12(12): 1371.
 [http://dx.doi.org/10.3390/v12121371] [PMID:  33266129]

[70]
de Castro Barbosa E, Alves TMA, Kohlhoff M, et al. Searching for plant-derived antivirals against dengue virus and Zika virus. Virol J  2022; 19(1): 31.
 [http://dx.doi.org/10.1186/s12985-022-01751-z] [PMID:  35193667]

[71]
Mottin M, Borba JVVB, Braga RC, et al. The A–Z of Zika drug discovery. Drug Discov Today  2018; 23(11): 1833-47.
 [http://dx.doi.org/10.1016/j.drudis.2018.06.014] [PMID:  29935345]

[72]
Rosa RL, Santi L, Berger M, et al. ZIKAVID—Zika virus infection database: A new platform to analyze the molecular impact of Zika virus infection. J Neurovirol  2020; 26(1): 77-83.
 [http://dx.doi.org/10.1007/s13365-019-00799-y] [PMID:  31512145]

[73]
Medina-Magües LG, Gergen J, Jasny E, et al. mRNA vaccine protects against zika virus. Vaccines  2021; 9(12): 1464.
 [http://dx.doi.org/10.3390/vaccines9121464] [PMID:  34960211]

[74]
Pereira RS, Santos FCP, Campana PRV, et al. Natural products and derivatives as potential zika virus inhibitors: A comprehensive review. Viruses  2023; 15(5): 1211.
 [http://dx.doi.org/10.3390/v15051211] [PMID:  37243296]

[75]
Chan JFW, Chik KKH, Yuan S, et al. Novel antiviral activity and mechanism of bromocriptine as a Zika virus NS2B-NS3 protease inhibitor. Antiviral Res  2017; 141: 29-37.
 [http://dx.doi.org/10.1016/j.antiviral.2017.02.002] [PMID:  28185815]

[76]
Cao B, Parnell LA, Diamond MS, Mysorekar IU. Inhibition of autophagy limits vertical transmission of Zika virus in pregnant mice. J Exp Med  2017; 214(8): 2303-13.
 [http://dx.doi.org/10.1084/jem.20170957] [PMID:  28694387]

[77]
Chiu CF, Chu LW, Liao IC, et al. The mechanism of the Zika virus crossing the placental barrier and the blood-brain barrier. Front Microbiol  2020; 11: 214.
 [http://dx.doi.org/10.3389/fmicb.2020.00214] [PMID:  32153526]

[78]
Zou M, Liu H, Li J, et al. Structure-activity relationship of flavonoid bifunctional inhibitors against Zika virus infection. Biochem Pharmacol  2020; 177: 113962.
 [http://dx.doi.org/10.1016/j.bcp.2020.113962] [PMID:  32272109]

[79]
Cataneo AHD, Kuczera D, Koishi AC. The citrus flavonoid naringenin impairs the in vitro infection of human cells by Zika virus. Sci Rep  2019; 9(1): 16348.
 [http://dx.doi.org/10.1038/s41598-019-52626-3]

[80]
Eberle RJ, Olivier DS, Pacca CC, et al. In vitro study of Hesperetin and Hesperidin as inhibitors of zika and chikungunya virus proteases. PLoS One  2021; 16(3): e0246319.
 [http://dx.doi.org/10.1371/journal.pone.0246319]

[81]
Sharma N, Murali A, Singh SK, Giri R. Epigallocatechin gallate, an active green tea compound inhibits the Zika virus entry into host cells via binding the envelope protein. Int J Biol Macromol  2017; 104(Pt A): 1046-54.
 [http://dx.doi.org/10.1016/j.ijbiomac.2017.06.105]

[82]
Lima CS, Mottin M, de Assis LR, et al. Flavonoids from Pterogyne nitens as Zika virus NS2B-NS3 protease inhibitors. Bioorg Chem  2021; 109: 104719.
 [http://dx.doi.org/10.1016/j.bioorg.2021.104719] [PMID:  33636437]

[83]
Rehman A, Ashfaq UA, Javed MR, Shahid F, Noor F, Aslam S. The screening of phytochemicals against NS5 polymerase to treat zika virus infection: Integrated computational based approach. Comb Chem High Throughput Screen  2022; 25(4): 738-51.
 [http://dx.doi.org/10.2174/1386207324666210712091920 ] [PMID:  34254908]

[84]
Thirumoorthy G, Tarachand SP, Nagella P, Veerappa Lakshmaiah V. Identification of potential ZIKV NS2B-NS3 protease inhibitors from Andrographis paniculata: An in silico approach. J Biomol Struct Dyn  2022; 40(21): 11203-15.
 [http://dx.doi.org/10.1080/07391102.2021.1956592 ] [PMID:  34319220]

[85]
Kumar S, El-Kafrawy SA, Bharadwaj S, et al. Discovery of bispecific lead compounds from azadirachta indica against ZIKA NS2B-NS3 protease and NS5 RNA dependent RNA polymerase using molecular simulations. Molecules  2022; 27(8): 2562.
 [http://dx.doi.org/10.3390/molecules27082562]

[86]
Ramos PRPDS, Mottin M, Lima CS, et al. Natural compounds as non-nucleoside inhibitors of zika virus polymerase through integration of in silico and in vitro approaches. Pharmaceuticals  2022; 15(12): 1493.
 [http://dx.doi.org/10.3390/ph15121493]

[87]
Mottin M, Caesar LK, Brodsky D, et al. Chalcones from Angelica keiskei (ashitaba) inhibit key Zika virus replication proteins. Bioorg Chem  2022; 120: 105649.
 [http://dx.doi.org/10.1016/j.bioorg.2022.105649] [PMID:  35124513]

[88]
Priya S, Kumar NS, Hemalatha S. Antiviral phytocompounds target envelop protein to control Zika virus. Comput Biol Chem  2018; 77: 402-12.
 [http://dx.doi.org/10.1016/j.compbiolchem.2018.08.008 ] [PMID:  30471642]

[89]
Sangeetha K, Martín-Acebes MA, Saiz JC, Meena KS. Molecular docking and antiviral activities of plant derived compounds against zika virus. Microb Pathog  2020; 149: 104540.
 [http://dx.doi.org/10.1016/j.micpath.2020.104540] [PMID:  33045342]

[90]
Lee JL, Loe MWC, Lee RCH, Chu JJH. Antiviral activity of pinocembrin against Zika virus replication. Antiviral Res  2019; 167: 13-24.
 [http://dx.doi.org/10.1016/j.antiviral.2019.04.003] [PMID:  30959074]

[91]
Zhu Y, Liang M, Yu J, et al. Repurposing of doramectin as a new anti-zika virus agent. Viruses  2023; 15(5): 1068.
 [http://dx.doi.org/10.3390/v15051068] [PMID:  37243154]

[92]
Oo A, Teoh BT, Sam SS, Bakar SA, Zandi K. Baicalein and baicalin as Zika virus inhibitors. Arch Virol  2019; 164(2): 585-93.
 [http://dx.doi.org/10.1007/s00705-018-4083-4] [PMID:  30392049]

[93]
Merino-Ramos T, Jiménez de Oya N, Saiz JC, Martín-Acebes MA. Antiviral activity of nordihydroguaiaretic acid and its derivative tetra- O -methyl nordihydroguaiaretic acid against west nile virus and zika virus. Antimicrob Agents Chemother  2017; 61(8): e00376-17.
 [http://dx.doi.org/10.1128/AAC.00376-17] [PMID:  28507114]

[94]
Barbosa-Lima G, Moraes AM, Araújo AS, et al. 2,8-bis(trifluoromethyl)quinoline analogs show improved anti-Zika virus activity, compared to mefloquine. Eur J Med Chem  2017; 127: 334-40.
 [http://dx.doi.org/10.1016/j.ejmech.2016.12.058] [PMID:  28068604]

[95]
Morales Vasquez D, Park JG, Ávila-Pérez G, et al. Identification of inhibitors of ZIKV replication. Viruses  2020; 12(9): 1041.
 [http://dx.doi.org/10.3390/v12091041] [PMID:  32961956]

[96]
Wong G, He S, Siragam V, et al. Antiviral activity of quercetin-3-β-O-D-glucoside against Zika virus infection. Virol Sin  2017; 32(6): 545-7.
 [http://dx.doi.org/10.1007/s12250-017-4057-9] [PMID:  28884445]

[97]
Gaudry A, Bos S, Viranaicken W, et al. The flavonoid isoquercitrin precludes initiation of zika virus infection in human cells. Int J Mol Sci  2018; 19(4): 1093.
 [http://dx.doi.org/10.3390/ijms19041093]

[98]
Lin SC, Chen MC, Liu S, et al. Phloretin inhibits Zika virus infection by interfering with cellular glucose utilisation. Int J Antimicrob Agents  2019; 54(1): 80-4.
 [http://dx.doi.org/10.1016/j.ijantimicag.2019.03.017 ] [PMID:  30930299]

[99]
Batista MN, Braga ACS, Campos GRF, et al. Natural products isolated from oriental medicinal herbs inactivate zika virus. Viruses  2019; 11(1): 49.
 [http://dx.doi.org/10.3390/v11010049]

[100]
Baltina LA, Lai HC, Liu YC, et al. Glycyrrhetinic acid derivatives as Zika virus inhibitors: Synthesis and antiviral activity in vitro. Bioorg Med Chem  2021; 41: 116204.
 [http://dx.doi.org/10.1016/j.bmc.2021.116204] [PMID:  34022526]

[101]
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]

[102]
Cui X, Zhou R, Huang C, et al. Identification of theaflavin-3,3′-digallate as a novel zika virus protease inhibitor. Front Pharmacol  2020; 11: 514313.
 [http://dx.doi.org/10.3389/fphar.2020.514313]

[103]
Ruchika G, Mona P, Yogendra S, Pankaj B, Rajat R. An overview of integrated risk factors with prevention and prevalence of asthma at the global level. Curr Tradit Med  2024; 10: e250523217358.
 [http://dx.doi.org/10.2174/2215083810666230525153908]

[104]
Ferraris P, Yssel H, Missé D. Zika virus infection: An update. Microbes Infect  2019; 21(8-9): 353-60.
 [http://dx.doi.org/10.1016/j.micinf.2019.04.005] [PMID:  31158508]

[105]
Pereira dos Santos MPC, Moll HC, Borella J, et al. Season and shading affect emetine and cephalin production in Carapichea ipecacuanha plants. Plant Biosyst  2022; 156(1): 51-60.
 [http://dx.doi.org/10.1080/11263504.2020.1832602]

[106]
Chen H, Lao Z, Xu J, et al. Antiviral activity of lycorine against Zika virus in vivo and in vitro. Virology  2020; 546: 88-97.
 [http://dx.doi.org/10.1016/j.virol.2020.04.009] [PMID:  32452420]

[107]
Martinez-Lopez A, Persaud M, Chavez MP, et al. Glycosylated diphyllin as a broad-spectrum antiviral agent against Zika virus. EBioMedicine  2019; 47: 269-83.
 [http://dx.doi.org/10.1016/j.ebiom.2019.08.060] [PMID:  31501074]

[108]
Zhou S, Lin Q, Huang C, et al. Rottlerin plays an antiviral role at early and late steps of Zika virus infection. Virol Sin  2022; 37(5): 685-94.
 [http://dx.doi.org/10.1016/j.virs.2022.07.012] [PMID:  35934227]

[109]
Vázquez-Calvo Á, Jiménez de Oya N, Martín-Acebes MA, Garcia-Moruno E, Saiz JC. Antiviral properties of the natural polyphenols delphinidin and epigallocatechin gallate against the flaviviruses west nile virus, zika virus, and dengue virus. Front Microbiol  2017; 8: 1314.
 [http://dx.doi.org/10.3389/fmicb.2017.01314] [PMID:  28744282]

[110]
Zhang C, Feng T, Cheng J, et al. Structure of the NS5 methyltransferase from Zika virus and implications in inhibitor design. Biochem Biophys Res Commun  2017; 492(4): 624-30.
 [http://dx.doi.org/10.1016/j.bbrc.2016.11.098] [PMID:  27866982]

[111]
G Viveiros Rosa S, Fierro IM, C Santos W. Repositioning and investigational drugs for Zika virus infection treatment: A patent review. Expert Opin Ther Pat  2020; 30(11): 847-62.
 [http://dx.doi.org/10.1080/13543776.2020.1811854 ] [PMID:  32842803]

[112]
Song W, Zhang H, Zhang Y, et al. Repurposing clinical drugs is a promising strategy to discover drugs against Zika virus infection. Front Med  2021; 15(3): 404-15.
 [http://dx.doi.org/10.1007/s11684-021-0834-9] [PMID:  33369711]

[113]
Karkhah A, Nouri HR, Javanian M, et al. Zika virus: Epidemiology, clinical aspects, diagnosis, and control of infection. Eur J Clin Microbiol Infect Dis  2018; 37(11): 2035-43.
 [http://dx.doi.org/10.1007/s10096-018-3354-z] [PMID:  30167886]

[114]
Munoz-Jordan JL. Diagnosis of Zika virus infections: Challenges and opportunities. J Infect Dis  2017; 216(S10): S951-6.
 [http://dx.doi.org/10.1093/infdis/jix502] [PMID:  29267922]

[115]
Zhang B, Pinsky BA, Ananta JS, et al. Diagnosis of Zika virus infection on a nanotechnology platform. Nat Med  2017; 23(5): 548-50.
 [http://dx.doi.org/10.1038/nm.4302] [PMID:  28263312]

[116]
Pena LJ, Miranda Guarines K, Duarte Silva AJ, et al. In vitro and in vivo models for studying Zika virus biology. J Gen Virol  2018; 99(12): 1529-50.
 [http://dx.doi.org/10.1099/jgv.0.001153] [PMID:  30325302]

[117]
Ohki CMY, Benazzato C, Russo FB, Beltrão-Braga PCB. Developing animal models of Zika virus infection for novel drug discovery. Expert Opin Drug Discov  2019; 14(6): 577-89.
 [http://dx.doi.org/10.1080/17460441.2019.1597050] [PMID:  30991850]

[118]
Miller MR, Fagre AC, Clarkson TC, Markle ED, Foy BD. Three immunocompetent small animal models that do not support zika virus infection. Pathogens  2021; 10(8): 971.
 [http://dx.doi.org/10.3390/pathogens10080971 ] [PMID:  34451435]
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DOI https://dx.doi.org/10.2174/0118715265272414231226092146	Print ISSN 1871-5265
Publisher Name Bentham Science Publisher	Online ISSN 2212-3989
Infectious Disorders - Drug Targets

Insight into the Natural Biomolecules (BMs): Promising Candidates as Zika Virus Inhibitors

Abstract

Graphical Abstract

New Frontiers in Infectious Disease Research: Small-Molecule Probes and Biomarker Identification

Infectious Disorders - Drug Targets

Insight into the Natural Biomolecules (BMs): Promising Candidates as Zika Virus Inhibitors

Abstract

Graphical Abstract

Call for Papers in Thematic Issues

New Frontiers in Infectious Disease Research: Small-Molecule Probes and Biomarker Identification

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