A Review on Structural Genomics Approach Applied for Drug Discovery Against Three Vector-borne Viral Diseases: Dengue, Chikungunya and Zika

Overview

Journal Virus Genes

Specialties Microbiology
Molecular Biology

Date 2022 Apr 8

PMID 35394596

Authors

Shobana Sundar

Shanmughavel Piramanayagam

Jeyakumar Natarajan

Affiliations

Soon will be listed here.

Abstract

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.

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References

Weigelt J, B McBroom-Cerajewski L, Schapira M, Zhao Y, Arrowsmith C, Arrowmsmith C . Structural genomics and drug discovery: all in the family. Curr Opin Chem Biol. 2008; 12(1):32-9. DOI: 10.1016/j.cbpa.2008.01.045. View

Stevens R, Yokoyama S, Wilson I . Global efforts in structural genomics. Science. 2001; 294(5540):89-92. DOI: 10.1126/science.1066011. View

Lundstrom K . Structural genomics for membrane proteins. Cell Mol Life Sci. 2006; 63(22):2597-607. PMC: 11136435. DOI: 10.1007/s00018-006-6252-y. View

Lundstrom K . Structural genomics of GPCRs. Trends Biotechnol. 2005; 23(2):103-8. DOI: 10.1016/j.tibtech.2004.12.006. View

Marsden B, Knapp S . Doing more than just the structure-structural genomics in kinase drug discovery. Curr Opin Chem Biol. 2008; 12(1):40-5. DOI: 10.1016/j.cbpa.2008.01.042. View

Zanotto P, Leite L . The Challenges Imposed by Dengue, Zika, and Chikungunya to Brazil. Front Immunol. 2018; 9:1964. PMC: 6121005. DOI: 10.3389/fimmu.2018.01964. View

Guzman M, Halstead S, Artsob H, Buchy P, Farrar J, Gubler D . Dengue: a continuing global threat. Nat Rev Microbiol. 2010; 8(12 Suppl):S7-16. PMC: 4333201. DOI: 10.1038/nrmicro2460. View

Modis Y, Ogata S, Clements D, Harrison S . A ligand-binding pocket in the dengue virus envelope glycoprotein. Proc Natl Acad Sci U S A. 2003; 100(12):6986-91. PMC: 165817. DOI: 10.1073/pnas.0832193100. View

Xia H, Xie X, Zou J, Noble C, Russell W, Holthauzen L . A cocrystal structure of dengue capsid protein in complex of inhibitor. Proc Natl Acad Sci U S A. 2020; 117(30):17992-18001. PMC: 7395448. DOI: 10.1073/pnas.2003056117. View

10.

Li L, Lok S, Yu I, Zhang Y, Kuhn R, Chen J . The flavivirus precursor membrane-envelope protein complex: structure and maturation. Science. 2008; 319(5871):1830-4. DOI: 10.1126/science.1153263. View

11.

Byrd C, Dai D, Grosenbach D, Berhanu A, Jones K, Cardwell K . A novel inhibitor of dengue virus replication that targets the capsid protein. Antimicrob Agents Chemother. 2012; 57(1):15-25. PMC: 3535982. DOI: 10.1128/AAC.01429-12. View

12.

Smith J, Sheridan K, Parkins C, Frueh L, Jemison A, Strode K . 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. 2018; 155:12-19. PMC: 9627977. DOI: 10.1016/j.antiviral.2018.04.019. View

13.

Schmidt A, Lee K, Yang P, Harrison S . Small-molecule inhibitors of dengue-virus entry. PLoS Pathog. 2012; 8(4):e1002627. PMC: 3320583. DOI: 10.1371/journal.ppat.1002627. View

14.

Yang J, Chen Y, Tu Y, Yen K, Yang Y . Combinatorial computational approaches to identify tetracycline derivatives as flavivirus inhibitors. PLoS One. 2007; 2(5):e428. PMC: 1855430. DOI: 10.1371/journal.pone.0000428. View

15.

Poh M, Yip A, Zhang S, Priestle J, Ma N, Smit J . A small molecule fusion inhibitor of dengue virus. Antiviral Res. 2009; 84(3):260-6. DOI: 10.1016/j.antiviral.2009.09.011. View

16.

Leal E, Adler N, Fernandez G, Gebhard L, Battini L, Aucar M . De novo design approaches targeting an envelope protein pocket to identify small molecules against dengue virus. Eur J Med Chem. 2019; 182:111628. DOI: 10.1016/j.ejmech.2019.111628. View

17.

Zhou Z, Khaliq M, Suk J, Patkar C, Li L, Kuhn R . Antiviral compounds discovered by virtual screening of small-molecule libraries against dengue virus E protein. ACS Chem Biol. 2008; 3(12):765-75. PMC: 2782732. DOI: 10.1021/cb800176t. View

18.

Kato D, Era S, Watanabe I, Arihara M, Sugiura N, Kimata K . Antiviral activity of chondroitin sulphate E targeting dengue virus envelope protein. Antiviral Res. 2010; 88(2):236-43. DOI: 10.1016/j.antiviral.2010.09.002. View

19.

Lin Y, Lei H, Lin Y, Yeh T, Chen S, Liu H . Heparin inhibits dengue-2 virus infection of five human liver cell lines. Antiviral Res. 2002; 56(1):93-6. DOI: 10.1016/s0166-3542(02)00095-5. View

20.

Hidari K, Takahashi N, Arihara M, Nagaoka M, Morita K, Suzuki T . Structure and anti-dengue virus activity of sulfated polysaccharide from a marine alga. Biochem Biophys Res Commun. 2008; 376(1):91-5. DOI: 10.1016/j.bbrc.2008.08.100. View