A review on structural genomics approach applied for drug discovery against three vector-borne viral diseases: Dengue, Chikungunya and Zika.
Chikungunya
Dengue
Structural genomics
Vector-borne viral diseases
Zika
Journal
Virus genes
ISSN: 1572-994X
Titre abrégé: Virus Genes
Pays: United States
ID NLM: 8803967
Informations de publication
Date de publication:
Jun 2022
Jun 2022
Historique:
received:
18
10
2021
accepted:
22
03
2022
pubmed:
9
4
2022
medline:
4
5
2022
entrez:
8
4
2022
Statut:
ppublish
Résumé
Structural genomics involves the advent of three-dimensional structures of the genome encoded proteins through various techniques available. Numerous structural genomics research groups have been developed across the globe and they contribute enormously to the identification of three-dimensional structures of various proteins. In this review, we have discussed the applications of the structural genomics approach towards the discovery of potential lead-like molecules against the genomic drug targets of three vector-borne diseases, namely, Dengue, Chikungunya and Zika. Currently, all these three diseases are associated with the most important global public health problems and significant economic burden in tropical countries. Structural genomics has accelerated the identification of novel drug targets and inhibitors for the treatment of these diseases. We start with the current development status of the drug targets and antiviral drugs against these three diseases and conclude by describing challenges that need to be addressed to overcome the shortcomings in the process of drug discovery.
Identifiants
pubmed: 35394596
doi: 10.1007/s11262-022-01898-5
pii: 10.1007/s11262-022-01898-5
doi:
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
151-171Subventions
Organisme : Indian Council of Medical Research
ID : ISRM/11(13)/2019
Informations de copyright
© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
Références
Weigelt J, McBroom-Cerajewski LD, Schapira M, Zhao Y, Arrowmsmith CH (2008) Structural genomics and drug discovery: all in the family. Curr Opin Chem Biol 12(1):32–39
pubmed: 18282486
doi: 10.1016/j.cbpa.2008.01.045
Stevens RC, Yokoyama S, Wilson IA (2001) Global efforts in structural genomics. Science 294(5540):89–92
pubmed: 11588249
doi: 10.1126/science.1066011
Lundstrom K (2006) Structural genomics for membrane proteins. Cell Mol Life Sci 63(22):2597–2607
pubmed: 17013556
doi: 10.1007/s00018-006-6252-y
Lundstrom K (2005) Structural genomics of GPCRs. Trends Biotechnol 23(2):103–108
pubmed: 15661348
doi: 10.1016/j.tibtech.2004.12.006
Marsden BD, Knapp S (2008) Doing more than just the structure—structural genomics in kinase drug discovery. Curr Opin Chem Biol 12(1):40–45
pubmed: 18267130
doi: 10.1016/j.cbpa.2008.01.042
https://www.who.int/news-room/fact-sheets/detail/vector-borne-diseases
Zanotto PM, Leite LC (2018) The challenges imposed by Dengue, Zika, and Chikungunya to Brazil. Front Immunol. https://doi.org/10.3389/fimmu.2018.01964
doi: 10.3389/fimmu.2018.01964
pubmed: 30210503
pmcid: 6121005
Guzman MG, Halstead SB, Artsob H, Buchy P, Farrar J, Gubler DJ, Hunsperger E, Kroeger A, Margolis HS, Martínez E, Nathan MB (2010) Dengue: a continuing global threat. Nat Rev Microbiol 8(12):S7-16
pubmed: 21079655
pmcid: 4333201
doi: 10.1038/nrmicro2460
Modis Y, Ogata S, Clements D, Harrison SC (2003) A ligand-binding pocket in the dengue virus envelope glycoprotein. Proc Natl Acad Sci 100(12):6986–6991
pubmed: 12759475
pmcid: 165817
doi: 10.1073/pnas.0832193100
Xia H, Xie X, Zou J, Noble CG, Russell WK, Holthauzen LM, Choi KH, White MA, Shi PY (2020) A cocrystal structure of dengue capsid protein in complex of inhibitor. Proc Natl Acad Sci 117(30):17992–18001
pubmed: 32669438
pmcid: 7395448
doi: 10.1073/pnas.2003056117
Li L, Lok SM, Yu IM, Zhang Y, Kuhn RJ, Chen J, Rossmann MG (2008) The flavivirus precursor membrane-envelope protein complex: structure and maturation. Science 319(5871):1830–1834
pubmed: 18369147
doi: 10.1126/science.1153263
Byrd CM, Dai D, Grosenbach DW, Berhanu A, Jones KF, Cardwell KB, Schneider C, Wineinger KA, Page JM, Harver C, Stavale E (2013) A novel inhibitor of dengue virus replication that targets the capsid protein. Antimicrob Agents Chemother 57(1):15–25
pubmed: 23070172
pmcid: 3535982
doi: 10.1128/AAC.01429-12
Smith JL, Sheridan K, Parkins CJ, Frueh L, Jemison AL, Strode K, Dow G, Nilsen A, Hirsch AJ (2018) Characterization and structure-activity relationship analysis of a class of antiviral compounds that directly bind dengue virus capsid protein and are incorporated into virions. Antiviral Res 155:12–19
pubmed: 29709563
doi: 10.1016/j.antiviral.2018.04.019
Schmidt AG, Lee K, Yang PL, Harrison SC (2012) Small-molecule inhibitors of dengue-virus entry. PLoS Pathog 8(4):e1002627
pubmed: 22496653
pmcid: 3320583
doi: 10.1371/journal.ppat.1002627
Yang JM, Chen YF, Tu YY, Yen KR, Yang YL (2007) Combinatorial computational approaches to identify tetracycline derivatives as flavivirus inhibitors. PLoS ONE 2(5):e428
pubmed: 17502914
pmcid: 1855430
doi: 10.1371/journal.pone.0000428
Poh MK, Yip A, Zhang S, Priestle JP, Ma NL, Smit JM, Wilschut J, Shi PY, Wenk MR, Schul W (2009) A small molecule fusion inhibitor of dengue virus. Antiviral Res 84(3):260–266
pubmed: 19800368
doi: 10.1016/j.antiviral.2009.09.011
Leal ES, Adler NS, Fernández GA, Gebhard LG, Battini L, Aucar MG, Videla M, Monge ME, de Los Ríos AH, Dávila JA, Morell ML (2019) De novo design approaches targeting an envelope protein pocket to identify small molecules against dengue virus. Eur J Med Chem 182:111628
pubmed: 31472473
doi: 10.1016/j.ejmech.2019.111628
Zhou Z, Khaliq M, Suk JE, Patkar C, Li L, Kuhn RJ, Post CB (2008) Antiviral compounds discovered by virtual screening of small-molecule libraries against dengue virus E protein. ACS Chem Biol 3(12):765–775
pubmed: 19053243
pmcid: 2782732
doi: 10.1021/cb800176t
Kato D, Era S, Watanabe I, Arihara M, Sugiura N, Kimata K, Suzuki Y, Morita K, Hidari KI, Suzuki T (2010) Antiviral activity of chondroitin sulphate E targeting dengue virus envelope protein. Antiviral Res 88(2):236–243
pubmed: 20851716
doi: 10.1016/j.antiviral.2010.09.002
Lin YL, Lei HY, Lin YS, Yeh TM, Chen SH, Liu HS (2002) Heparin inhibits dengue-2 virus infection of five human liver cell lines. Antiviral Res 56(1):93–96
pubmed: 12323403
doi: 10.1016/S0166-3542(02)00095-5
Hidari KI, Takahashi N, Arihara M, Nagaoka M, Morita K, Suzuki T (2008) Structure and anti-dengue virus activity of sulfated polysaccharide from a marine alga. Biochem Biophys Res Commun 376(1):91–95
pubmed: 18762172
doi: 10.1016/j.bbrc.2008.08.100
Talarico LB, Damonte EB (2007) Interference in dengue virus adsorption and uncoating by carrageenans. Virology 363(2):473–485
pubmed: 17337028
doi: 10.1016/j.virol.2007.01.043
Lee E, Pavy M, Young N, Freeman C, Lobigs M (2006) Antiviral effect of the heparan sulfate mimetic, PI-88, against dengue and encephalitic flaviviruses. Antiviral Res 69(1):31–38
pubmed: 16309754
doi: 10.1016/j.antiviral.2005.08.006
Lin LT, Chen TY, Lin SC, Chung CY, Lin TC, Wang GH, Anderson R, Lin CC, Richardson CD (2013) Broad-spectrum antiviral activity of chebulagic acid and punicalagin against viruses that use glycosaminoglycans for entry. BMC Microbiol 13(1):1–5
doi: 10.1186/1471-2180-13-1
Faustino AF, Guerra GM, Huber RG, Hollmann A, Domingues MM, Barbosa GM, Enguita FJ, Bond PJ, Castanho MA, Da Poian AT, Almeida FC (2015) Understanding dengue virus capsid protein disordered N-terminus and pep14-23-based inhibition. ACS Chem Biol 10(2):517–526
pubmed: 25412346
doi: 10.1021/cb500640t
Balinsky CA, Schmeisser H, Ganesan S, Singh K, Pierson TC, Zoon KC (2013) Nucleolin interacts with the dengue virus capsid protein and plays a role in formation of infectious virus particles. J Virol 87(24):13094–13106
pubmed: 24027323
pmcid: 3838225
doi: 10.1128/JVI.00704-13
Qin CF, Qin ED (2004) Development of cell lines stably expressing staphylococcal nuclease fused to dengue 2 virus capsid protein for CTVI. Acta Biochim Biophys Sin 36(8):577–582
pubmed: 15295652
doi: 10.1093/abbs/36.8.577
Schmidt AG, Yang PL, Harrison SC (2010) Peptide inhibitors of dengue-virus entry target a late-stage fusion intermediate. PLoS Pathog 6(4):e1000851
pubmed: 20386713
pmcid: 2851732
doi: 10.1371/journal.ppat.1000851
Hrobowski YM, Garry RF, Michael SF (2005) Peptide inhibitors of dengue virus and West Nile virus infectivity. Virology J 2(1):1
doi: 10.1186/1743-422X-2-49
Isa DM, Chin SP, Chong WL, Zain SM, Abd Rahman N, Lee VS (2019) Dynamics and binding interactions of peptide inhibitors of dengue virus entry. J Biol Phys 45(1):63–76
pubmed: 30680580
pmcid: 6408556
doi: 10.1007/s10867-018-9515-6
Costin JM, Jenwitheesuk E, Lok SM, Hunsperger E, Conrads KA, Fontaine KA, Rees CR, Rossmann MG, Isern S, Samudrala R, Michael SF (2010) Structural optimization and de novo design of dengue virus entry inhibitory peptides. PLoS Negl Trop Dis 4(6):e721
pubmed: 20582308
pmcid: 2889824
doi: 10.1371/journal.pntd.0000721
Panya A, Sawasdee N, Junking M, Srisawat C, Choowongkomon K, Yenchitsomanus PT (2015) A peptide inhibitor derived from the conserved ectodomain region of DENV membrane (M) protein with activity against dengue virus infection. Chem Biol Drug Des 86(5):1093–1104
pubmed: 25891143
doi: 10.1111/cbdd.12576
Edeling MA, Diamond MS, Fremont DH (2014) Structural basis of Flavivirus NS1 assembly and antibody recognition. Proc Natl Acad Sci 111(11):4285–4290
pubmed: 24594604
pmcid: 3964132
doi: 10.1073/pnas.1322036111
Libraty DH, Young PR, Pickering D, Endy TP, Kalayanarooj S, Green S et al (2002) High circulating levels of the dengue virus nonstructural protein NS1 early in dengue illness correlate with the development of dengue hemorrhagic fever. J Infect Dis 186(8):1165–1168. https://doi.org/10.1086/343813
doi: 10.1086/343813
pubmed: 12355369
Songprakhon P, Thaingtamtanha T, Limjindaporn T, Puttikhunt C, Srisawat C, Luangaram P, Dechtawewat T, Uthaipibull C, Thongsima S, Yenchitsomanus PT, Malasit P (2020) Peptides targeting dengue viral nonstructural protein 1 inhibit dengue virus production. Sci Rep 10(1):1–6
doi: 10.1038/s41598-020-69515-9
Chandramouli S, Joseph JS, Daudenarde S, Gatchalian J, Cornillez-Ty C, Kuhn P (2010) Serotype-specific structural differences in the protease-cofactor complexes of the dengue virus family. J Virol 84(6):3059–3067
pubmed: 20042502
doi: 10.1128/JVI.02044-09
Rothan HA, Han HC, Ramasamy TS, Othman S, Abd Rahman N, Yusof R (2012) Inhibition of dengue NS2B-NS3 protease and viral replication in Vero cells by recombinant retrocyclin-1. BMC Infect Dis 12(1):1–9
doi: 10.1186/1471-2334-12-314
Yang CC, Hu HS, Wu RH, Wu SH, Lee SJ, Jiaang WT, Chern JH, Huang ZS, Wu HN, Chang CM, Yueh A (2014) A novel dengue virus inhibitor, BP13944, discovered by high-throughput screening with dengue virus replicon cells selects for resistance in the viral NS2B/NS3 protease. Antimicrob Agents Chemother 58(1):110–119
pubmed: 24145533
pmcid: 3910792
doi: 10.1128/AAC.01281-13
Tomlinson SM, Malmstrom RD, Russo A, Mueller N, Pang YP, Watowich SJ (2009) Structure-based discovery of dengue virus protease inhibitors. Antiviral Res 82(3):110–114
pubmed: 19428601
pmcid: 2680748
doi: 10.1016/j.antiviral.2009.02.190
Matusan AE, Pryor MJ, Davidson AD, Wright PJ (2001) Mutagenesis of the Dengue virus type 2 NS3 protein within and outside helicase motifs: effects on enzyme activity and virus replication. J Virol 75(20):9633–9643
pubmed: 11559795
pmcid: 114534
doi: 10.1128/JVI.75.20.9633-9643.2001
Swarbrick CM, Basavannacharya C, Chan KW, Chan SA, Singh D, Wei N, Phoo WW, Luo D, Lescar J, Vasudevan SG (2017) NS3 helicase from dengue virus specifically recognizes viral RNA sequence to ensure optimal replication. Nucleic Acids Res 45(22):12904–12920
pubmed: 29165589
pmcid: 5728396
doi: 10.1093/nar/gkx1127
Mastrangelo E, Pezzullo M, De Burghgraeve T, Kaptein S, Pastorino B, Dallmeier K, de Lamballerie X, Neyts J, Hanson AM, Frick DN, Bolognesi M (2012) Ivermectin is a potent inhibitor of flavivirus replication specifically targeting NS3 helicase activity: new prospects for an old drug. J Antimicrob Chemother 67(8):1884–1894
pubmed: 22535622
pmcid: 3888155
doi: 10.1093/jac/dks147
Byrd CM, Grosenbach DW, Berhanu A, Dai D, Jones KF, Cardwell KB, Schneider C, Yang G, Tyavanagimatt S, Harver C, Wineinger KA (2013) Novel benzoxazole inhibitor of dengue virus replication that targets the NS3 helicase. Antimicrob Agents Chemother 57(4):1902–1912
pubmed: 23403421
pmcid: 3623359
doi: 10.1128/AAC.02251-12
Basavannacharya C, Vasudevan SG (2014) Suramin inhibits helicase activity of NS3 protein of dengue virus in a fluorescence-based high throughput assay format. Biochem Biophys Res Commun 453(3):539–544
pubmed: 25281902
doi: 10.1016/j.bbrc.2014.09.113
Norazharuddin H, Lai NS (2018) Roles and prospects of dengue virus non-structural proteins as antiviral targets: an easy digest. Malays J Med Sci 25(5):6
pubmed: 30914859
pmcid: 6419879
van Cleef KW, Overheul GJ, Thomassen MC, Marjakangas JM, van Rij RP (2016) Escape mutations in NS4B render dengue virus insensitive to the antiviral activity of the paracetamol metabolite AM404. Antimicrob Agents Chemother 60(4):2554–2557
pubmed: 26856827
pmcid: 4808173
doi: 10.1128/AAC.02462-15
Xie X, Wang QY, Xu HY, Qing M, Kramer L, Yuan Z, Shi PY (2011) Inhibition of dengue virus by targeting viral NS4B protein. J Virol 85(21):11183–11195
pubmed: 21865382
pmcid: 3194949
doi: 10.1128/JVI.05468-11
Nguyen NM, Tran CN, Phung LK, Duong KT, Huynh HL, Farrar J, Nguyen QT, Tran HT, Nguyen CV, Merson L, Hoang LT (2013) A randomized, double-blind placebo controlled trial of balapiravir, a polymerase inhibitor, in adult dengue patients. J Infect Dis 207(9):1442–1450
pubmed: 22807519
doi: 10.1093/infdis/jis470
Carocci M, Hinshaw SM, Rodgers MA, Villareal VA, Burri DJ, Pilankatta R, Maharaj NP, Gack MU, Stavale EJ, Warfield KL, Yang PL (2015) The bioactive lipid 4-hydroxyphenyl retinamide inhibits flavivirus replication. Antimicrob Agents Chemother 59(1):85–95
pubmed: 25313218
doi: 10.1128/AAC.04177-14
Yokokawa F, Nilar S, Noble CG, Lim SP, Rao R, Tania S, Wang G, Lee G, Hunziker J, Karuna R, Manjunatha U (2016) Discovery of potent non-nucleoside inhibitors of dengue viral RNA-dependent RNA polymerase from a fragment hit using structure-based drug design. J Med Chem 59(8):3935–3952
pubmed: 26984786
doi: 10.1021/acs.jmedchem.6b00143
Lim SP, Noble CG, Nilar S, Shi PY, Yokokawa F (2018) Discovery of potent non-nucleoside inhibitors of dengue viral RNA-dependent RNA polymerase from fragment screening and structure-guided design. Dengue Zika: Control Antivir Treat Strateg. https://doi.org/10.1007/978-981-10-8727-1_14
doi: 10.1007/978-981-10-8727-1_14
Benmansour F, Trist I, Coutard B, Decroly E, Querat G, Brancale A, Barral K (2017) Discovery of novel dengue virus NS5 methyltransferase non-nucleoside inhibitors by fragment-based drug design. Eur J Med Chem 125:865–880
pubmed: 27750202
doi: 10.1016/j.ejmech.2016.10.007
Haese N, Powers J, Streblow DN (2020) Small molecule inhibitors targeting chikungunya virus. Chikungunya Virus. https://doi.org/10.1007/82_2020_195
doi: 10.1007/82_2020_195
Sharma R, Fatma B, Saha A, Bajpai S, Sistla S, Dash PK, Parida M, Kumar P, Tomar S (2016) Inhibition of chikungunya virus by picolinate that targets viral capsid protein. Virology 498:265–276
pubmed: 27614702
doi: 10.1016/j.virol.2016.08.029
Kumar R, Nehul S, Singh A, Tomar S (2021) Identification and evaluation of antiviral potential of thymoquinone, a natural compound targeting Chikungunya virus capsid protein. Virology 561:36–46
pubmed: 34146962
doi: 10.1016/j.virol.2021.05.013
Sharma R, Kesari P, Kumar P, Tomar S (2018) Structure-function insights into chikungunya virus capsid protein: small molecules targeting capsid hydrophobic pocket. Virology 515:223–234
pubmed: 29306785
doi: 10.1016/j.virol.2017.12.020
Fatma B, Kumar R, Singh VA, Nehul S, Sharma R, Kesari P, Kuhn RJ, Tomar S (2020) Alphavirus capsid protease inhibitors as potential antiviral agents for Chikungunya infection. Antiviral Res 179:104808
pubmed: 32380148
doi: 10.1016/j.antiviral.2020.104808
Weber C, Berberich E, von Rhein C, Henß L, Hildt E, Schnierle BS (2017) Identification of functional determinants in the chikungunya virus E2 protein. PLoS Negl Trop Dis 11(1):e0005318
pubmed: 28114368
pmcid: 5289616
doi: 10.1371/journal.pntd.0005318
Uchime O, Fields W, Kielian M (2013) The role of E3 in pH protection during alphavirus assembly and exit. J Virol 87(18):10255–10262
pubmed: 23864626
pmcid: 3754015
doi: 10.1128/JVI.01507-13
Voss JE, Vaney MC, Duquerroy S, Vonrhein C, Girard-Blanc C, Crublet E, Thompson A, Bricogne G, Rey FA (2010) Glycoprotein organization of Chikungunya virus particles revealed by X-ray crystallography. Nature 468(7324):709–712
pubmed: 21124458
doi: 10.1038/nature09555
Nguyen PT, Yu H, Keller PA (2018) Molecular docking studies to explore potential binding pockets and inhibitors for chikungunya virus envelope glycoproteins. Interdiscip Sci: Comput Life Sci 10(3):515–524
doi: 10.1007/s12539-016-0209-0
Passos GF, Gomes MG, Aquino TM, Araújo-Júnior JX, Souza SJ, Cavalcante JP, Santos EC, Bassi ÊJ, Silva-Júnior EF (2020) Computer-aided design, synthesis, and antiviral evaluation of novel acrylamides as potential inhibitors of E3-E2-E1 glycoproteins complex from Chikungunya virus. Pharmaceuticals 13(7):141
pmcid: 7407227
doi: 10.3390/ph13070141
Islamuddin M, Afzal O, Khan WH, Hisamuddin M, Altamimi AS, Husain I, Kato K, Alamri MA, Parveen S (2021) Inhibition of Chikungunya Virus Infection by 4-Hydroxy-1-Methyl-3-(3-morpholinopropanoyl) quinoline-2 (1 H)-one (QVIR) Targeting nsP2 and E2 Proteins. ACS Omega 6(14):9791–9803
pubmed: 33869959
pmcid: 8047676
doi: 10.1021/acsomega.1c00447
Dey D, Siddiqui SI, Mamidi P, Ghosh S, Kumar CS, Chattopadhyay S, Ghosh S, Banerjee M (2019) The effect of amantadine on an ion channel protein from Chikungunya virus. PLoS Negl Trop Dis 13(7):e0007548
pubmed: 31339886
pmcid: 6655611
doi: 10.1371/journal.pntd.0007548
Rupp JC, Sokoloski KJ, Gebhart NN, Hardy RW (2015) Alphavirus RNA synthesis and non-structural protein functions. J Gen Virol 96(Pt 9):2483
pubmed: 26219641
pmcid: 4635493
doi: 10.1099/jgv.0.000249
Feibelman KM, Fuller BP, Li L, LaBarbera DV, Geiss BJ (2018) Identification of small molecule inhibitors of the Chikungunya virus nsP1 RNA capping enzyme. Antivir Res 154:124–131
pubmed: 29680670
doi: 10.1016/j.antiviral.2018.03.013
Gigante A, Canela MD, Delang L, Priego EM, Camarasa MJ, Querat G, Neyts J, Leyssen P, Pérez-Pérez MJ (2014) Identification of [1, 2, 3] triazolo [4, 5-d] pyrimidin-7 (6 H)-ones as novel inhibitors of Chikungunya virus replication. J Med Chem 57(10):4000–4008
pubmed: 24800626
doi: 10.1021/jm401844c
Mudgal R, Mahajan S, Tomar S (2020) Inhibition of Chikungunya virus by an adenosine analog targeting the SAM-dependent nsP1 methyltransferase. FEBS Lett 594(4):678–694
pubmed: 31623018
doi: 10.1002/1873-3468.13642
Kovacikova K, Morren BM, Tas A, Albulescu IC, van Rijswijk R, Jarhad DB, Shin YS, Jang MH, Kim G, Lee HW, Jeong LS (2020) 6′-β-Fluoro-homoaristeromycin and 6′-fluoro-homoneplanocin A are potent inhibitors of chikungunya virus replication through their direct effect on viral nonstructural protein 1. Antimicrob Agents Chemother 64(4):e02532-e2619
pubmed: 31964798
pmcid: 7179274
doi: 10.1128/AAC.02532-19
Moesslacher J, Battisti V, Delang L, Neyts J, Abdelnabi R, Pürstinger G, Urban E, Langer T (2020) Identification of 2-(4-(phenylsulfonyl) piperazine-1-yl) pyrimidine analogues as novel inhibitors of chikungunya virus. ACS Med Chem Lett 11(5):906–912
pubmed: 32435404
pmcid: 7236252
doi: 10.1021/acsmedchemlett.9b00662
Zhang K, Law YS, Law MC, Tan YB, Wirawan M, Luo D (2021) Structural insights into viral RNA capping and plasma membrane targeting by Chikungunya virus nonstructural protein 1. Cell Host Microbe 29(5):757–764
pubmed: 33730549
doi: 10.1016/j.chom.2021.02.018
Kovacikova K, Gorostiola González M, Jones R, Reguera J, Gigante A, Pérez-Pérez MJ, Pürstinger G, Moesslacher J, Langer T, Jeong LS, Delang L (2021) Structural insights into the mechanisms of action of functionally distinct classes of Chikungunya virus nonstructural protein 1 inhibitors. Antimicrob Agents Chemother 65(7):e02566-e2620
pmcid: 8218635
doi: 10.1128/AAC.02566-20
Fros JJ, van der Maten E, Vlak JM, Pijlman GP (2013) The C-terminal domain of chikungunya virus nsP2 independently governs viral RNA replication, cytopathicity, and inhibition of interferon signaling. J Virol 87(18):10394–10400
pubmed: 23864632
pmcid: 3753987
doi: 10.1128/JVI.00884-13
Narwal M, Singh H, Pratap S, Malik A, Kuhn RJ, Kumar P, Tomar S (2018) Crystal structure of chikungunya virus nsP2 cysteine protease reveals a putative flexible loop blocking its active site. Int J Biol Macromol 116:451–462
pubmed: 29730006
doi: 10.1016/j.ijbiomac.2018.05.007
Bassetto M, De Burghgraeve T, Delang L, Massarotti A, Coluccia A, Zonta N, Gatti V, Colombano G, Sorba G, Silvestri R, Tron GC (2013) Computer-aided identification, design and synthesis of a novel series of compounds with selective antiviral activity against chikungunya virus. Antivir Res 98(1):12–18
pubmed: 23380636
doi: 10.1016/j.antiviral.2013.01.002
Nguyen PT, Yu H, Keller PA (2015) Identification of chikungunya virus nsP2 protease inhibitors using structure-base approaches. J Mol Graph Model 57:1–8
pubmed: 25622129
doi: 10.1016/j.jmgm.2015.01.001
Agarwal T, Asthana S, Bissoyi A (2015) Molecular modeling and docking study to elucidate novel chikungunya virus nsP2 protease inhibitors. Indian J Pharm Sci 77(4):453
pubmed: 26664062
pmcid: 4649777
doi: 10.4103/0250-474X.164769
Jain J, Kumari A, Somvanshi P, Grover A, Pai S, Sunil S (2017) In silico analysis of natural compounds targeting structural and nonstructural proteins of chikungunya virus. F1000Research 6:1601
pubmed: 29333236
pmcid: 5747330
doi: 10.12688/f1000research.12301.2
Kumar P, Kumar D, Giri R (2019) Targeting the nsp2 cysteine protease of chikungunya virus using FDA approved library and selected cysteine protease inhibitors. Pathogens 8(3):128
pmcid: 6789655
doi: 10.3390/pathogens8030128
Meena MK, Kumar D, Kumari K, Kaushik NK, Kumar RV, Bahadur I, Vodwal L, Singh P (2021) Promising inhibitors of nsp2 of CHIKV using molecular docking and temperature-dependent molecular dynamics simulations. J Biomol Struct Dyn. https://doi.org/10.1080/07391102.2021.1873863
doi: 10.1080/07391102.2021.1873863
pubmed: 34662249
Rasool N, Bakht A, Hussain W (2021) Analysis of inhibitor binding combined with reactivity studies to discover the potentially inhibiting phytochemicals targeting Chikungunya viral replication. Curr Drug Discov Technol 18(3):437–450
pubmed: 32164512
doi: 10.2174/1570163817666200312102659
Lani R, Agharbaoui FE, Hassandarvish P, Teoh BT, Sam SS, Zandi K, Rahman NA, AbuBakar S (2021) In silico studies of fisetin and silymarin as novel chikungunya virus nonstructural proteins inhibitors. Future Virol 16(3):167–180
doi: 10.2217/fvl-2019-0090
Singh Jadav S, Nayan Sinha B, Pastorino B, de Lamballerie X, Hilgenfeld R, Jayaprakash V (2015) Identification of pyrazole derivative as an antiviral agent against Chikungunya through HTVS. Lett Drug Des Discov 12(4):292–301
doi: 10.2174/1570180811666141001005402
Das PK, Puusepp L, Varghese FS, Utt A, Ahola T, Kananovich DG, Lopp M, Merits A, Karelson M (2016) Design and validation of novel chikungunya virus protease inhibitors. Antimicrob Agents Chemother 60(12):7382–7395
pubmed: 27736770
pmcid: 5119020
doi: 10.1128/AAC.01421-16
Ivanova L, Rausalu K, Žusinaite E, Tammiku-Taul J, Merits A, Karelson M (2021) 1, 3-Thiazolbenzamide derivatives as Chikungunya virus nsP2 protease inhibitors. ACS Omega 6(8):5786–5794
pubmed: 33681617
pmcid: 7931429
doi: 10.1021/acsomega.0c06191
Eberle RJ, Olivier DS, Pacca CC, Avilla CM, Nogueira ML, Amaral MS, Willbold D, Arni RK, Coronado MA (2021) In vitro study of Hesperetin and Hesperidin as inhibitors of zika and chikungunya virus proteases. PLoS ONE 16(3):e0246319
pubmed: 33661906
pmcid: 7932080
doi: 10.1371/journal.pone.0246319
Tripathi PK, Soni A, Yadav SP, Kumar A, Gaurav N, Raghavendhar S, Sharma P, Sunil S, Jayaram B, Patel AK (2020) Evaluation of novobiocin and telmisartan for anti-CHIKV activity. Virology 548:250–260
pubmed: 32791353
doi: 10.1016/j.virol.2020.05.010
Tripathi PK, Singh J, Gaurav N, Garg DK, Patel AK (2020) In-silico and biophysical investigation of biomolecular interaction between naringin and nsP2 of the chikungunya virus. Int J Biol Macromol 160:1061–1065
pubmed: 32464207
doi: 10.1016/j.ijbiomac.2020.05.165
Singh H, Mudgal R, Narwal M, Kaur R, Singh VA, Malik A, Chaudhary M, Tomar S (2018) Chikungunya virus inhibition by peptidomimetic inhibitors targeting virus-specific cysteine protease. Biochimie 149:51–61
pubmed: 29635044
doi: 10.1016/j.biochi.2018.04.004
El-labbad EM, Ismail MA, Abou Ei Ella DA, Ahmed M, Wang F, Barakat KH, Abouzid KA (2015) Discovery of novel peptidomimetics as irreversible CHIKV Ns P 2 protease inhibitors using quantum mechanical-based ligand descriptors. Chem Biol Drug Des 86(6):1518–1527
pubmed: 26212366
doi: 10.1111/cbdd.12621
Law YS, Utt A, Tan YB, Zheng J, Wang S, Chen MW, Griffin PR, Merits A, Luo D (2019) Structural insights into RNA recognition by the Chikungunya virus nsP2 helicase. Proc Natl Acad Sci 116(19):9558–9567
pubmed: 31000599
pmcid: 6511008
doi: 10.1073/pnas.1900656116
Abraham R, Hauer D, McPherson RL, Utt A, Kirby IT, Cohen MS, Merits A, Leung AK, Griffin DE (2018) ADP-ribosyl–binding and hydrolase activities of the alphavirus nsP3 macrodomain are critical for initiation of virus replication. Proc Natl Acad Sci 115(44):E10457–E10466
pubmed: 30322911
pmcid: 6217424
doi: 10.1073/pnas.1812130115
Malet H, Coutard B, Jamal S, Dutartre H, Papageorgiou N, Neuvonen M, Ahola T, Forrester N, Gould EA, Lafitte D, Ferron F (2009) The crystal structures of Chikungunya and Venezuelan equine encephalitis virus nsP3 macro domains define a conserved adenosine binding pocket. J Virol 83(13):6534–6545
pubmed: 19386706
pmcid: 2698539
doi: 10.1128/JVI.00189-09
Zhang S, Garzan A, Haese N, Bostwick R, Martinez-Gzegozewska Y, Rasmussen L, Streblow DN, Haise MT, Pathak AK, Augelli-Szafran CE, Wu M (2021) Pyrimidone inhibitors targeting Chikungunya Virus nsP3 macrodomain by fragment-based drug design. PLoS ONE 16(1):e0245013
pubmed: 33482665
pmcid: 7822648
doi: 10.1371/journal.pone.0245013
Shimizu JF, Martins DO, McPhillie MJ, Roberts GC, Zothner C, Merits A, Harris M, Jardim AC (2020) Is the ADP ribose site of the Chikungunya virus NSP3 Macro domain a target for antiviral approaches? Acta Trop 207:105490
pubmed: 32333884
doi: 10.1016/j.actatropica.2020.105490
Nguyen PT, Yu H, Keller PA (2014) Discovery of in silico hits targeting the nsP3 macro domain of chikungunya virus. J Mol Model 20(5):1–2
doi: 10.1007/s00894-014-2216-6
Kumar D, Kumari K, Jayaraj A, Singh P (2020) Development of a theoretical model for the inhibition of nsP3 protease of Chikungunya virus using pyranooxazoles. J Biomol Struct Dyn 38(10):3018–3034
pubmed: 31366291
doi: 10.1080/07391102.2019.1650830
Meena MK, Kumar D, Jayaraj A, Kumar A, Kumari K, Katata-Seru LM, Bahadur I, Kumar V, Sherawat A, Singh P (2020) Designed thiazolidines: an arsenal for the inhibition of nsP3 of CHIKV using molecular docking and MD simulations. J Biomol Struct Dyn. https://doi.org/10.1080/07391102.2020.1832918
doi: 10.1080/07391102.2020.1832918
pubmed: 33073705
Kumar D, Meena MK, Kumari K, Patel R, Jayaraj A, Singh P (2020) In-silico prediction of novel drug-target complex of nsp3 of CHIKV through molecular dynamic simulation. Heliyon 6(8):e04720
pubmed: 32904235
pmcid: 7452467
doi: 10.1016/j.heliyon.2020.e04720
Chaudhary M, Sehgal D (2021) In silico identification of natural antiviral compounds as a potential inhibitor of chikungunya virus non-structural protein 3 macrodomain. J Biomol Struct Dyn. https://doi.org/10.1080/07391102.2021.1960195
doi: 10.1080/07391102.2021.1960195
pubmed: 34931595
pmcid: 8171009
Patil P, Agrawal M, Almelkar S, Jeengar MK, More A, Alagarasu K, Kumar NV, Mainkar PS, Parashar D, Cherian S (2021) In vitro and in vivo studies reveal α-Mangostin, a xanthonoid from Garcinia mangostana, as a promising natural antiviral compound against chikungunya virus. Virol J 18(1):1–2
doi: 10.1186/s12985-021-01517-z
LaStarza MW, Lemm JA, Rice CM (1994) Genetic analysis of the nsP3 region of Sindbis virus: evidence for roles in minus-strand and subgenomic RNA synthesis. J Virol 68(9):5781–5791
pubmed: 8057460
pmcid: 236982
doi: 10.1128/jvi.68.9.5781-5791.1994
Nandi I, Gupta A, Chaudhary VK, Gupta V, Gabrani R, Gupta S (2019) Expression, purification and functional characterization of recombinant hypervariable region (HVR) of Chikungunya virus nsP3 protein. 3 Biotech 9(6):1–8
doi: 10.1007/s13205-019-1759-8
Satheesh G, Prabhu PN, Venkataramana M (2014) 3D Modeling of dengue virus NS4B and Chikungunya virus nsP4: identification of a common drug target and designing a single antiviral inhibitor. Curr Comput Aided Drug Des 10(4):361–373
pubmed: 25847003
doi: 10.2174/1573409911666150407161535
Reyes-Gastellou A, Jiménez-Alberto A, Castelán-Vega JA, Aparicio-Ozores G, Ribas-Aparicio RM (2021) Chikungunya nsP4 homology modeling reveals a common motif with Zika and Dengue RNA polymerases as a potential therapeutic target. J Mol Model 27(9):1–2
doi: 10.1007/s00894-021-04868-0
Wada Y, Orba Y, Sasaki M, Kobayashi S, Carr MJ, Nobori H, Sato A, Hall WW, Sawa H (2017) Discovery of a novel antiviral agent targeting the nonstructural protein 4 (nsP4) of chikungunya virus. Virology 505:102–112
pubmed: 28236746
doi: 10.1016/j.virol.2017.02.014
Ehteshami M, Tao S, Zandi K, Hsiao HM, Jiang Y, Hammond E, Amblard F, Russell OO, Merits A, Schinazi RF (2017) Characterization of β-d-N 4-hydroxycytidine as a novel inhibitor of chikungunya virus. Antimicrob Agents Chemother 61(4):e02395-e2416
pubmed: 28137799
pmcid: 5365705
doi: 10.1128/AAC.02395-16
Ferreira AC, Reis PA, de Freitas CS, Sacramento CQ, Villas Bôas Hoelz L, Bastos MM, Mattos M, Rocha N, Gomes de Azevedo Quintanilha I, da Silva Gouveia Pedrosa C, Rocha Quintino Souza L (2019) Beyond members of the Flaviviridae family, sofosbuvir also inhibits chikungunya virus replication. Antimicrob Agents Chemother 63(2):e01389-18
pubmed: 30455237
pmcid: 6355571
doi: 10.1128/AAC.01389-18
Kumar SP, Kapopara RG, Patni MI, Pandya HA, Jasrai YT, Patel SK (2012) Exploring the polymerase activity of chikungunya viral non structural protein 4 (nsP4) using molecular modeling, epharmacophore and docking studies. Int J Pharm Life Sci 3(6):1752–1765
Ghildiyal R, Gupta S, Gabrani R, Joshi G, Gupta A, Chaudhary VK, Gupta V (2019) In silico study of chikungunya polymerase, a potential target for inhibitors. Virusdisease 30(3):394–402
pubmed: 31803807
pmcid: 6864021
doi: 10.1007/s13337-019-00547-0
Ayres CF, Guedes DR, Paiva MH, Morais-Sobral MC, Krokovsky L, Machado LC, Melo-Santos MA, Crespo M, Oliveira CM, Ribeiro RS, Cardoso OA (2019) Zika virus detection, isolation and genome sequencing through Culicidae sampling during the epidemic in Vitória, Espírito Santo, Brazil. Parasit Vectors 12(1):220
pubmed: 31068218
pmcid: 6505216
doi: 10.1186/s13071-019-3461-4
Shang Z, Song H, Shi Y, Qi J, Gao GF (2018) Crystal structure of the capsid protein from Zika virus. J Mol Biol 430(7):948–962
pubmed: 29454707
doi: 10.1016/j.jmb.2018.02.006
Ahmed SR, Banik A, Anni SM, Chowdhury MM (2020) Plant derived bioactive compounds as potential inhibitors of ZIKA virus: an in silico investigation. bioRxiv. https://doi.org/10.1101/2020.11.11.378083
doi: 10.1101/2020.11.11.378083
pubmed: 32793903
pmcid: 7418717
Dai L, Song J, Lu X, Deng YQ, Musyoki AM, Cheng H, Zhang Y, Yuan Y, Song H, Haywood J, Xiao H (2016) Structures of the Zika virus envelope protein and its complex with a flavivirus broadly protective antibody. Cell Host Microbe 19(5):696–704
pubmed: 27158114
doi: 10.1016/j.chom.2016.04.013
Fernando S, Fernando T, Stefanik M, Eyer L, Ruzek D (2016) An approach for Zika virus inhibition using homology structure of the envelope protein. Mol Biotechnol 58(12):801–806
pubmed: 27683255
doi: 10.1007/s12033-016-9979-1
Carneiro BM, Batista MN, Braga AC, Nogueira ML, Rahal P (2016) The green tea molecule EGCG inhibits Zika virus entry. Virology 496:215–218
pubmed: 27344138
doi: 10.1016/j.virol.2016.06.012
Barrows NJ, Campos RK, Powell ST, Prasanth KR, Schott-Lerner G, Soto-Acosta R, Galarza-Muñoz G, McGrath EL, Urrabaz-Garza R, Gao J, Wu P (2016) A screen of FDA-approved drugs for inhibitors of Zika virus infection. Cell Host Microbe 20(2):259–270
pubmed: 27476412
pmcid: 4993926
doi: 10.1016/j.chom.2016.07.004
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
pubmed: 28343845
doi: 10.1016/j.antiviral.2017.03.014
Rausch K, Hackett BA, Weinbren NL, Reeder SM, Sadovsky Y, Hunter CA, Schultz DC, Coyne CB, Cherry S (2017) Screening bioactives reveals nanchangmycin as a broad spectrum antiviral active against Zika virus. Cell Rep 18(3):804
pubmed: 28099856
pmcid: 5270376
doi: 10.1016/j.celrep.2016.12.068
Röcker AE, Müller JA, Dietzel E, Harms M, Krüger F, Heid C, Sowislok A, Riber CF, Kupke A, Lippold S, von Einem J (2018) The molecular tweezer CLR01 inhibits Ebola and Zika virus infection. Antiviral Res 152:26–35
pubmed: 29428508
pmcid: 7113745
doi: 10.1016/j.antiviral.2018.02.003
Oo A, Teoh BT, Sam SS, Bakar SA, Zandi K (2019) Baicalein and baicalin as Zika virus inhibitors. Adv Virol 164(2):585–593
Gao Y, Tai W, Wang N, Li X, Jiang S, Debnath AK, Du L, Chen S (2019) Identification of novel natural products as effective and broad-spectrum anti-Zika virus inhibitors. Viruses 11(11):1019
pmcid: 6893700
doi: 10.3390/v11111019
Telehany SM, Humby MS, McGee TD Jr, Riley SP, Jacobs A, Rizzo RC (2020) Identification of Zika virus inhibitors using homology modeling and similarity-based screening to target glycoprotein E. Biochemistry 59(39):3709–3724
pubmed: 32876433
doi: 10.1021/acs.biochem.0c00458
Pitts J, Hsia CY, Lian W, Wang J, Pfeil MP, Kwiatkowski N, Li Z, Jang J, Gray NS, Yang PL (2019) Identification of small molecule inhibitors targeting the Zika virus envelope protein. Antivir Res 164:147–153
pubmed: 30771406
doi: 10.1016/j.antiviral.2019.02.008
Sharma N, Prosser O, Kumar P, Tuplin A, Giri R (2020) Small molecule inhibitors possibly targeting the rearrangement of Zika virus envelope protein. Antivir Res 182:104876
pubmed: 32783901
doi: 10.1016/j.antiviral.2020.104876
Zou M, Liu H, Li J, Yao X, Chen Y, Ke C, Liu S (2020) Structure-activity relationship of flavonoid bifunctional inhibitors against Zika virus infection. Biochem Pharmacol 177:113962
pubmed: 32272109
doi: 10.1016/j.bcp.2020.113962
Yu Y, Deng YQ, Zou P, Wang Q, Dai Y, Yu F, Du L, Zhang NN, Tian M, Hao JN, Meng Y (2017) A peptide-based viral inactivator inhibits Zika virus infection in pregnant mice and fetuses. Nat Commun 8(1):1–2
doi: 10.1038/s41467-016-0009-6
Chen L, Liu Y, Wang S, Sun J, Wang P, Xin Q, Zhang L, Xiao G, Wang W (2017) Antiviral activity of peptide inhibitors derived from the protein E stem against Japanese encephalitis and Zika viruses. Antivir Res 141:140–149
pubmed: 28232248
doi: 10.1016/j.antiviral.2017.02.009
Wang D, Chen C, Liu S, Zhou H, Yang K, Zhao Q, Ji X, Chen C, Xie W, Wang Z, Mi LZ (2017) A mutation identified in neonatal microcephaly destabilizes Zika virus NS1 assembly in vitro. Sci Rep 7(1):1
pubmed: 28127051
pmcid: 5428335
doi: 10.1038/s41598-016-0028-x
Raza S, Abbas G, Azam SS (2019) Screening pipeline for Flavivirus based inhibitors for Zika virus NS1. IEEE/ACM Trans Comput Biol Bioinform 17(5):1751–1761
pubmed: 30990437
doi: 10.1109/TCBB.2019.2911081
Ahmad N, Badshah SL, Junaid M, Ur Rehman A, Muhammad A, Khan K (2021) Structural insights into the Zika virus NS1 protein inhibition using a computational approach. J Biomol Struct Dyn 39(8):3004–3011
pubmed: 32321364
doi: 10.1080/07391102.2020.1759453
Erbel P, Schiering N, D’Arcy A, Renatus M, Kroemer M, Lim SP, Yin Z, Keller TH, Vasudevan SG, Hommel U (2006) Structural basis for the activation of flaviviral NS3 proteases from dengue and West Nile virus. Nat Struct Mol Biol 13(4):372–373
pubmed: 16532006
doi: 10.1038/nsmb1073
Lei J, Hansen G, Nitsche C, Klein CD, Zhang L, Hilgenfeld R (2016) Crystal structure of Zika virus NS2B-NS3 protease in complex with a boronate inhibitor. Science 353(6298):503–505
pubmed: 27386922
doi: 10.1126/science.aag2419
Yuan S, Chan JF, den Haan H, Chik KK, Zhang AJ, Chan CC, Poon VK, Yip CC, Mak WW, Zhu Z, Zou Z (2017) Structure-based discovery of clinically approved drugs as Zika virus NS2B-NS3 protease inhibitors that potently inhibit Zika virus infection in vitro and in vivo. Antivir Res 145:33–43
pubmed: 28712942
doi: 10.1016/j.antiviral.2017.07.007
Roy A, Lim L, Srivastava S, Lu Y, Song J (2017) Solution conformations of Zika NS2B-NS3pro and its inhibition by natural products from edible plants. PLoS ONE 12(7):e0180632
pubmed: 28700665
pmcid: 5503262
doi: 10.1371/journal.pone.0180632
Li Z, Brecher M, Deng YQ, Zhang J, Sakamuru S, Liu B, Huang R, Koetzner CA, Allen CA, Jones SA, Chen H (2017) Existing drugs as broad-spectrum and potent inhibitors for Zika virus by targeting NS2B-NS3 interaction. Cell Res 27(8):1046–1064
pubmed: 28685770
pmcid: 5539352
doi: 10.1038/cr.2017.88
Lee H, Ren J, Nocadello S, Rice AJ, Ojeda I, Light S, Minasov G, Vargas J, Nagarathnam D, Anderson WF, Johnson ME (2017) Identification of novel small molecule inhibitors against NS2B/NS3 serine protease from Zika virus. Antivir Res 139:49–58
pubmed: 28034741
doi: 10.1016/j.antiviral.2016.12.016
Lim HJ, Nguyen TT, Kim NM, Park JS, Jang TS, Kim D (2017) Inhibitory effect of flavonoids against NS2B-NS3 protease of ZIKA virus and their structure activity relationship. Biotechnol Lett 39(3):415–421
pubmed: 27885509
doi: 10.1007/s10529-016-2261-6
Chan JF, Chik KK, Yuan S, Yip CC, Zhu Z, Tee KM, Tsang JO, Chan CC, Poon VK, Lu G, Zhang AJ (2017) Novel antiviral activity and mechanism of bromocriptine as a Zika virus NS2B-NS3 protease inhibitor. Antivir Res 141:29–37
pubmed: 28185815
doi: 10.1016/j.antiviral.2017.02.002
Li Y, Zhang Z, Phoo WW, Loh YR, Li R, Yang HY, Jansson AE, Hill J, Keller TH, Nacro K, Luo D (2018) Structural insights into the inhibition of Zika virus NS2B-NS3 protease by a small-molecule inhibitor. Structure 26(4):555–564
pubmed: 29526431
doi: 10.1016/j.str.2018.02.005
Kumar A, Liang B, Aarthy M, Singh SK, Garg N, Mysorekar IU, Giri R (2018) Hydroxychloroquine inhibits Zika virus NS2B-NS3 protease. ACS Omega 3(12):18132–18141
pubmed: 30613818
pmcid: 6312647
doi: 10.1021/acsomega.8b01002
Coronado MA, Eberle RJ, Bleffert N, Feuerstein S, Olivier DS, de Moraes FR, Willbold D, Arni RK (2018) Zika virus NS2B/NS3 proteinase: a new target for an old drug-Suramin a lead compound for NS2B/NS3 proteinase inhibition. Antivir Res 160:118–125
pubmed: 30393012
doi: 10.1016/j.antiviral.2018.10.019
Li Z, Sakamuru S, Huang R, Brecher M, Koetzner CA, Zhang J, Chen H, Qin CF, Zhang QY, Zhou J, Kramer LD (2018) Erythrosin B is a potent and broad-spectrum orthosteric inhibitor of the flavivirus NS2B-NS3 protease. Antivir Res 150:217–225
pubmed: 29288700
doi: 10.1016/j.antiviral.2017.12.018
Santos FR, Nunes DA, Lima WG, Davyt D, Santos LL, Taranto AG, Ferreira MSJ (2019) Identification of Zika virus NS2B-NS3 protease inhibitors by structure-based virtual screening and drug repurposing approaches. J Chem Inf Model 60(2):731–737
pubmed: 31850756
doi: 10.1021/acs.jcim.9b00933
Yao Y, Huo T, Lin YL, Nie S, Wu F, Hua Y, Wu J, Kneubehl AR, Vogt MB, Rico-Hesse R, Song Y (2019) Discovery, X-ray crystallography and antiviral activity of allosteric inhibitors of flavivirus NS2B-NS3 protease. J Am Chem Soc 141(17):6832–6836
pubmed: 31017399
pmcid: 6501818
doi: 10.1021/jacs.9b02505
Rassias G, Zogali V, Swarbrick CM, Chan KW, Chan SA, Gwee CP, Wang S, Kaplanai E, Canko A, Kiousis D, Lescar J (2019) Cell-active carbazole derivatives as inhibitors of the Zika virus protease. Eur J Med Chem 180:536–545
pubmed: 31344613
doi: 10.1016/j.ejmech.2019.07.007
Pathak N, Kuo YP, Chang TY, Huang CT, Hung HC, Hsu JT, Yu GY, Yang JM (2020) Zika virus NS3 protease pharmacophore anchor model and drug discovery. Sci Rep 10(1):1–7
doi: 10.1038/s41598-019-56847-4
Cui X, Zhou R, Huang C, Zhang R, Wang J, Zhang Y, Ding J, Li X, Zhou J, Cen S (2020) Identification of theaflavin-3, 3’-digallate as a novel Zika virus protease inhibitor. Front Pharmacol. https://doi.org/10.3389/fphar.2020.514313
doi: 10.3389/fphar.2020.514313
pubmed: 34267651
pmcid: 7774101
Pach S, Sarter TM, Yousef R, Schaller D, Bergemann S, Arkona C, Rademann J, Nitsche C, Wolber G (2020) Catching a moving target: comparative modeling of flaviviral NS2B-NS3 reveals small molecule Zika protease inhibitors. ACS Med Chem Lett 11(4):514–520
pubmed: 32292558
pmcid: 7153273
doi: 10.1021/acsmedchemlett.9b00629
Voss S, Nitsche C (2020) Inhibitors of the Zika virus protease NS2B-NS3. Bioorg Med Chem Lett 30(5):126965
pubmed: 31980339
doi: 10.1016/j.bmcl.2020.126965
Akaberi D, Chinthakindi PK, Båhlström A, Palanisamy N, Sandström A, Lundkvist Å, Lennerstrand J (2020) Identification of a C2-symmetric diol based human immunodeficiency virus protease inhibitor targeting Zika virus NS2B-NS3 protease. J Biomol Struct Dyn 38(18):5526–5536
pubmed: 31880199
doi: 10.1080/07391102.2019.1704882
Coluccia A, Puxeddu M, Nalli M, Wei CK, Wu YH, Mastrangelo E, Elamin T, Tarantino D, Bugert JJ, Schreiner B, Nolte J (2020) Discovery of Zika virus NS2B/NS3 inhibitors that prevent mice from life-threatening infection and brain damage. ACS Med Chem Lett 11(10):1869–1874
pubmed: 33062166
pmcid: 7549096
doi: 10.1021/acsmedchemlett.9b00405
Lima CS, Mottin M, de Assis LR, Mesquita NC, de Paula Sousa BK, Coimbra LD, Bispo-dos-Santos K, Zorn KM, Guido RV, Ekins S, Marques RE (2021) Flavonoids from Pterogyne nitens as Zika virus NS2B-NS3 protease inhibitors. Bioorg Chem 109:104719
pubmed: 33636437
pmcid: 8227833
doi: 10.1016/j.bioorg.2021.104719
Nie S, Yao Y, Wu F, Wu X, Zhao J, Hua Y, Wu J, Huo T, Lin YL, Kneubehl AR, Vogt MB (2021) Synthesis, structure–activity relationships, and antiviral activity of allosteric inhibitors of Flavivirus NS2B–NS;3 protease. J Med Chem 64(5):2777–2800
pubmed: 33596380
pmcid: 8052950
doi: 10.1021/acs.jmedchem.0c02070
Nie S, Zhao J, Wu X, Yao Y, Wu F, Lin YL, Li X, Kneubehl AR, Vogt MB, Rico-Hesse R, Song Y (2021) Synthesis, structure-activity relationship and antiviral activity of indole-containing inhibitors of Flavivirus NS2B-NS3 protease. Eur J Med Chem 225:113767
pubmed: 34450494
doi: 10.1016/j.ejmech.2021.113767
Chong Teoh T, Al-Harbi JS, Abdulrahman AY, Rothan HA (2021) Doxycycline interferes with Zika virus serine protease and inhibits virus replication in human skin fibroblasts. Molecules 26(14):4321
pubmed: 34299596
pmcid: 8306286
doi: 10.3390/molecules26144321
Shiryaev SA, Farhy C, Pinto A, Huang CT, Simonetti N, Ngono AE, Dewing A, Shresta S, Pinkerton AB, Cieplak P, Strongin AY (2017) Characterization of the Zika virus two-component NS2B-NS3 protease and structure-assisted identification of allosteric small-molecule antagonists. Antivir Res 143:218–229
pubmed: 28461069
doi: 10.1016/j.antiviral.2017.04.015
Nitsche C, Zhang L, Weigel LF, Schilz J, Graf D, Bartenschlager R, Hilgenfeld R, Klein CD (2017) Peptide–boronic acid inhibitors of flaviviral proteases: medicinal chemistry and structural biology. J Med Chem 60(1):511–516
pubmed: 27966962
doi: 10.1021/acs.jmedchem.6b01021
Jackman JA, Costa VV, Park S, Real AL, Park JH, Cardozo PL, Ferhan AR, Olmo IG, Moreira TP, Bambirra JL, Queiroz VF (2018) Therapeutic treatment of Zika virus infection using a brain-penetrating antiviral peptide. Nat Mater 17(11):971–977
pubmed: 30349030
doi: 10.1038/s41563-018-0194-2
Phoo WW, Zhang Z, Wirawan M, Chew EJ, Chew AB, Kouretova J, Steinmetzer T, Luo D (2018) Structures of Zika virus NS2B-NS3 protease in complex with peptidomimetic inhibitors. Antivir Res 160:17–24
pubmed: 30315877
doi: 10.1016/j.antiviral.2018.10.006
Nitsche C, Passioura T, Varava P, Mahawaththa MC, Leuthold MM, Klein CD, Suga H, Otting G (2019) De novo discovery of nonstandard macrocyclic peptides as noncompetitive inhibitors of the Zika virus NS2B-NS3 protease. ACS Med Chem Lett 10(2):168–174
pubmed: 30783498
pmcid: 6378662
doi: 10.1021/acsmedchemlett.8b00535
Abdulrahman AY, Khazali AS, Teoh TC, Rothan HA, Yusof R (2019) Novel peptides inhibit zika NS2B-NS3 serine protease and virus replication in human hepatic cell line. Int J Pept Res Ther 25(4):1659–1668
doi: 10.1007/s10989-019-09808-4
Sahoo M, Lingaraja Jena SD, Kumar S (2016) Virtual screening for potential inhibitors of NS3 protein of Zika virus. Genom Inform 14(3):104
doi: 10.5808/GI.2016.14.3.104
Byler KG, Ogungbe IV, Setzer WN (2016) In-silico screening for anti-Zika virus phytochemicals. J Mol Graph Model 69:78–91
pubmed: 27588363
pmcid: 7185537
doi: 10.1016/j.jmgm.2016.08.011
Fatima M, Khan MS, Rashid H, Mehmood A, Kanwal S, Rasheed MA, Jamil F (2018) Structure based virtual screening and molecular docking studies for identification of allosteric inhibitors against Zika virus protease NS2B-NS3. Pak J Zool 50(5):1709–1715
doi: 10.17582/journal.pjz/2018.50.5.1709.1715
Rohini K, Agarwal P, Preethi B, Shanthi V, Ramanathan K (2019) Exploring the lead compounds for Zika virus NS2B-NS3 protein: an e-pharmacophore-based approach. Appl Biochem Biotechnol 187(1):194–210
pubmed: 29911269
doi: 10.1007/s12010-018-2814-3
Bowen LR, Li DJ, Nola DT, Anderson MO, Heying M, Groves AT, Eagon S (2019) Identification of potential Zika virus NS2B-NS3 protease inhibitors via docking, molecular dynamics and consensus scoring-based virtual screening. J Mol Model 25(7):1
doi: 10.1007/s00894-019-4076-6
Choudhry H, Alzahrani FA, Hassan MA, Alghamdi A, Abdulaal WH, Bakhrebah MA, Zamzami MA, Helmi N, Bokhari FF, Zeyadi M, Baothman OA (2019) Zika virus targeting by screening inhibitors against NS2B/NS3 protease. Biomed Res Int. https://doi.org/10.1155/2019/3947245
doi: 10.1155/2019/3947245
pubmed: 31886207
pmcid: 6893251
Thirumoorthy GS, Tarachand SP, Nagella P, Veerappa Lakshmaiah V (2021) Identification of potential ZIKV NS2B-NS3 protease inhibitors from Andrographis paniculata: an in-silico approach. J Biomol Struct Dyn. https://doi.org/10.1080/07391102.2021.1956592
doi: 10.1080/07391102.2021.1956592
pubmed: 34319220
Shin HJ, Kim MH, Lee JY, Hwang I, Yoon GY, Kim HS, Kwon YC, Ahn DG, Kim KD, Kim BT, Kim SJ (2021) Structure-based virtual screening: identification of a novel NS2B-NS3 protease inhibitor with potent antiviral activity against Zika and Dengue viruses. Microorganisms 9(3):545
pubmed: 33800763
pmcid: 8000814
doi: 10.3390/microorganisms9030545
Zhao B, Yi G, Du F, Chuang YC, Vaughan RC, Sankaran B, Kao CC, Li P (2017) Structure and function of the Zika virus full-length NS5 protein. Nat Commun 8(1):1–9
doi: 10.1038/s41467-016-0009-6
Zmurko J, Marques RE, Schols D, Verbeken E, Kaptein SJ, Neyts J (2016) The viral polymerase inhibitor 7-deaza-2’-C-methyladenosine is a potent inhibitor of in vitro Zika virus replication and delays disease progression in a robust mouse infection model. PLoS Negl Trop Dis 10(5):e0004695
pubmed: 27163257
pmcid: 4862633
doi: 10.1371/journal.pntd.0004695
Xu HT, Hassounah SA, Colby-Germinario SP, Oliveira M, Fogarty C, Quan Y, Han Y, Golubkov O, Ibanescu I, Brenner B, Stranix BR (2017) Purification of Zika virus RNA-dependent RNA polymerase and its use to identify small-molecule Zika inhibitors. J Antimicrob Chemother 72(3):727–734
pubmed: 28069884
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
pubmed: 27902933
doi: 10.1016/j.antiviral.2016.11.023
Wang C, Yang SN, Smith K, Forwood JK, Jans DA (2017) Nuclear import inhibitor N-(4-hydroxyphenyl) retinamide targets Zika virus (ZIKV) nonstructural protein 5 to inhibit ZIKV infection. Biochem Biophys Res Commun 493(4):1555–1559
pubmed: 28988109
doi: 10.1016/j.bbrc.2017.10.016
Lu G, Bluemling GR, Collop P, Hager M, Kuiper D, Gurale BP, Painter GR, De La Rosa A, Kolykhalov AA (2017) Analysis of ribonucleotide 5′-triphosphate analogs as potential inhibitors of Zika virus RNA-dependent RNA polymerase by using nonradioactive polymerase assays. Antimicrob Agents Chemother 61(3):e01967-e2016
pubmed: 27993851
pmcid: 5328514
doi: 10.1128/AAC.01967-16
Tong X, Smith J, Bukreyeva N, Koma T, Manning JT, Kalkeri R, Kwong AD, Paessler S (2018) Merimepodib, an IMPDH inhibitor, suppresses replication of Zika virus and other emerging viral pathogens. Antivir Res 149:34–40
pubmed: 29126899
doi: 10.1016/j.antiviral.2017.11.004
Yang S, Xu M, Lee EM, Gorshkov K, Shiryaev SA, He S, Sun W, Cheng YS, Hu X, Tharappel AM, Lu B (2018) Emetine inhibits Zika and Ebola virus infections through two molecular mechanisms: inhibiting viral replication and decreasing viral entry. Cell Discov 4(1):1–4
doi: 10.1038/s41421-018-0068-4
Pattnaik A, Palermo N, Sahoo BR, Yuan Z, Hu D, Annamalai AS, Vu HL, Correas I, Prathipati PK, Destache CJ, Li Q (2018) Discovery of a non-nucleoside RNA polymerase inhibitor for blocking Zika virus replication through in silico screening. Antivir Res 151:78–86
pubmed: 29274845
doi: 10.1016/j.antiviral.2017.12.016
Lin Y, Zhang H, Song W, Si S, Han Y, Jiang J (2019) Identification and characterization of Zika virus NS5 RNA-dependent RNA polymerase inhibitors. Int J Antimicrob Agents 54(4):502–506
pubmed: 31310806
doi: 10.1016/j.ijantimicag.2019.07.010
Gharbi-Ayachi A, Santhanakrishnan S, Wong YH, Chan KW, Tan ST, Bates RW, Vasudevan SG, El Sahili A, Lescar J (2020) Non-nucleoside inhibitors of Zika virus RNA-dependent RNA polymerase. J Virol 94(21):e00794-e820
pubmed: 32796069
pmcid: 7565630
doi: 10.1128/JVI.00794-20
Yuan J, Yu J, Huang Y, He Z, Luo J, Wu Y, Zheng Y, Wu J, Zhu X, Wang H, Li M (2020) Antibiotic fidaxomicin is an RdRp inhibitor as a potential new therapeutic agent against Zika virus. BMC Med 18(1):1–6
doi: 10.1186/s12916-020-01663-1
Chen Y, Li Z, Pan P, Lao Z, Xu J, Li Z, Zhan S, Liu X, Wu Y, Wang W, Li G (2021) Cinnamic acid inhibits Zika virus by inhibiting RdRp activity. Antivir Res 192:105117
pubmed: 34174248
doi: 10.1016/j.antiviral.2021.105117
Sáez-Álvarez Y, Jiménez de Oya N, Del Águila C, Saiz JC, Arias A, Agudo R, Martín-Acebes MA (2021) Novel non-nucleoside inhibitors of Zika virus polymerase identified through the screening of an open library of anti-kynetoplastid compounds. Antimicrob Agents Chemother. https://doi.org/10.1128/AAC.00894-21
doi: 10.1128/AAC.00894-21
pubmed: 34152807
pmcid: 8370225
Stephen P, Baz M, Boivin G, Lin SX (2016) Structural insight into NS5 of Zika virus leading to the discovery of MTase inhibitors. J Am Chem Soc 138(50):16212–16215
pubmed: 27998085
doi: 10.1021/jacs.6b10399
Hercik K, Brynda J, Nencka R, Boura E (2017) Structural basis of Zika virus methyltransferase inhibition by sinefungin. Adv Virol 162(7):2091–2096
Hernandez J, Hoffer L, Coutard B, Querat G, Roche P, Morelli X, Decroly E, Barral K (2019) Optimization of a fragment linking hit toward Dengue and Zika virus NS5 methyltransferases inhibitors. Eur J Med Chem 161:323–333
pubmed: 30368131
doi: 10.1016/j.ejmech.2018.09.056
Spizzichino S, Mattedi G, Lauder K, Valle C, Aouadi W, Canard B, Decroly E, Kaptein SJ, Neyts J, Graham C, Sule Z (2020) Design, synthesis and discovery of N, N’-carbazoyl-aryl-urea Inhibitors of Zika NS5 methyltransferase and virus replication. ChemMedChem 15(4):385
pubmed: 31805205
pmcid: 7106487
doi: 10.1002/cmdc.201900533
Song W, Zhang H, Zhang Y, Chen Y, Lin Y, Han Y, Jiang J (2021) Identification and characterization of Zika Virus NS5 methyltransferase inhibitors. Front Cell Infect Microbiol 11:267
Elfiky AA (2016) Zika viral polymerase inhibition using anti-HCV drugs both in market and under clinical trials. J Med Virol 88(12):2044–2051
pubmed: 27604059
doi: 10.1002/jmv.24678
Singh A, Jana NK (2017) Discovery of potential Zika virus RNA polymerase inhibitors by docking-based virtual screening. Comput Biol Chem 71:144–151
pubmed: 29096380
doi: 10.1016/j.compbiolchem.2017.10.007
Ramharack P, Soliman ME (2018) Zika virus NS5 protein potential inhibitors: an enhanced in silico approach in drug discovery. J Biomol Struct Dyn 36(5):1118–1133
pubmed: 28351337
doi: 10.1080/07391102.2017.1313175
Elfiky AA (2020) Novel guanosine derivatives against Zika virus polymerase in silico. J Med Virol 92(1):11–16
pubmed: 31436327
doi: 10.1002/jmv.25573
Ali R, Badshah SL, Faheem M, Abbasi SW, Ullah R, Bari A, Jamal SB, Mahmood HM, Haider A, Haider S (2020) Identification of potential inhibitors of Zika virus NS5 RNA-dependent RNA polymerase through virtual screening and molecular dynamic simulations. Saudi Pharm J 28(12):1580–1591
pubmed: 33424251
pmcid: 7783101
doi: 10.1016/j.jsps.2020.10.005
Zhang C, Feng T, Cheng J, Li Y, Yin X, Zeng W, Jin X, Li Y, Guo F, Jin T (2017) Structure of the NS5 methyltransferase from Zika virus and implications in inhibitor design. Biochem Biophys Res Commun 492(4):624–630
pubmed: 27866982
doi: 10.1016/j.bbrc.2016.11.098
Santos FR, Lima WG, Maia EH, Assis LC, Davyt D, Taranto AG, Ferreira JM (2020) Identification of a potential Zika virus inhibitor targeting NS5 methyltransferase using virtual screening and molecular dynamics simulations. J Chem Inf Model 60(2):562–568
pubmed: 31985225
doi: 10.1021/acs.jcim.9b00809
Bharadwaj S, Rao AK, Dwivedi VD, Mishra SK, Yadava U (2021) Structure-based screening and validation of bioactive compounds as Zika virus methyltransferase (MTase) inhibitors through first-principle density functional theory, classical molecular simulation and QM/MM affinity estimation. J Biomol Struct Dyn 39(7):2338–2351
pubmed: 32216596
doi: 10.1080/07391102.2020.1747545
Kingwell K (2021) Pan-serotype antiviral for dengue infection. Nat Rev Microbiol 19(4):221
pubmed: 33649578
doi: 10.1038/s41579-021-00538-3
Scroggs SL, Gass JT, Chinnasamy R, Widen SG, Azar SR, Rossi SL, Arterburn JB, Vasilakis N, Hanley KA (2021) Evolution of resistance to fluoroquinolones by dengue virus serotype 4 provides insight into mechanism of action and consequences for viral fitness. Virology 552:94–106
pubmed: 33120225
doi: 10.1016/j.virol.2020.09.004