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Published in: Journal of Natural Medicines 4/2015

Open Access 01-10-2015 | Mini-Review

Chikungunya virus (CHIKV) inhibitors from natural sources: a medicinal chemistry perspective

Authors: Soumendranath Bhakat, Mahmoud E. S. Soliman

Published in: Journal of Natural Medicines | Issue 4/2015

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Abstract

Chikungunya virus (CHIKV) is one of the re-emerging “neglected” tropical diseases whose recent outbreak affected not only Africa and South-East Asia but also several parts of America and Europe. To date, despite its serious nature, no antivirals or vaccines were developed in order to counter this resurgent infectious disease. The recent advancement in crystallography and availability of crystal structures of certain domains of CHIKV initiates the development of anti-CHIKV agents using structure-based drug design or synthetic medicinal chemistry approach. Despite the fact that almost 50 % of the new chemical entities against several biological targets were either obtained from natural products or natural product analogues, a very humble effort was directed towards identification of novel CHIKV inhibitors from natural products. In this review, besides a brief overview on CHIKV as well as the nature as a source of medicines, we highlight the current progress and future steps towards the discovery of CHIKV inhibitors from natural products. This report could pave the road towards the design of novel semi-synthetic derivatives with enhanced anti-viral activities.

Graphical Abstract

Literature
1.
go back to reference Rashad AA, Mahalingam S, Keller PA (2014) Chikungunya virus: emerging targets and new opportunities for medicinal chemistry. J Med Chem 57:1147–1166CrossRefPubMed Rashad AA, Mahalingam S, Keller PA (2014) Chikungunya virus: emerging targets and new opportunities for medicinal chemistry. J Med Chem 57:1147–1166CrossRefPubMed
2.
go back to reference Belov GA (2014) Modulation of lipid synthesis and trafficking pathways by picornaviruses. Curr Opin Virol 9:19–23CrossRefPubMed Belov GA (2014) Modulation of lipid synthesis and trafficking pathways by picornaviruses. Curr Opin Virol 9:19–23CrossRefPubMed
3.
go back to reference Hirneisen K, Reith JL, Wei J, Hoover DG, Hicks DT, Pivarnik LF, Kniel KE (2014) Comparison of pressure inactivation of caliciviruses and picornaviruses in a model food system. Innov Food Sci Emerg Technol 26:102–107CrossRef Hirneisen K, Reith JL, Wei J, Hoover DG, Hicks DT, Pivarnik LF, Kniel KE (2014) Comparison of pressure inactivation of caliciviruses and picornaviruses in a model food system. Innov Food Sci Emerg Technol 26:102–107CrossRef
5.
go back to reference Koehn FE, Carter GT (2005) The evolving role of natural products in drug discovery. Nat Rev Drug Discov 4:206–220CrossRefPubMed Koehn FE, Carter GT (2005) The evolving role of natural products in drug discovery. Nat Rev Drug Discov 4:206–220CrossRefPubMed
6.
go back to reference Li JW, Vederas JC (2009) Drug discovery and natural products: end of an era or an endless frontier? Science 325:161–165CrossRefPubMed Li JW, Vederas JC (2009) Drug discovery and natural products: end of an era or an endless frontier? Science 325:161–165CrossRefPubMed
7.
go back to reference Molinari G (2009) Natural products in drug discovery: present status and perspectives. Adv Exp Med Biol 655:13–27CrossRefPubMed Molinari G (2009) Natural products in drug discovery: present status and perspectives. Adv Exp Med Biol 655:13–27CrossRefPubMed
8.
go back to reference Molinari G (2009) Natural products in drug discovery: present status and perspectives. In: Guzman CA, Feuerstein GZ (eds) Pharmaceutical biotechnology. Springer, New York, pp 13–27CrossRef Molinari G (2009) Natural products in drug discovery: present status and perspectives. In: Guzman CA, Feuerstein GZ (eds) Pharmaceutical biotechnology. Springer, New York, pp 13–27CrossRef
9.
go back to reference Li JWH, Vederas JC (2009) Drug discovery and natural products: end of an era or an endless frontier? Science 325:161–165CrossRefPubMed Li JWH, Vederas JC (2009) Drug discovery and natural products: end of an era or an endless frontier? Science 325:161–165CrossRefPubMed
10.
go back to reference Teixeira RR, Pereira WL, da Silveira Costa, Oliveira AF, da Silva AM, de Oliveira AS, da Silva ML, da Silva CC, de Paula SO (2014) Natural products as source of potential dengue antivirals. Molecules 19:8151–8176CrossRefPubMed Teixeira RR, Pereira WL, da Silveira Costa, Oliveira AF, da Silva AM, de Oliveira AS, da Silva ML, da Silva CC, de Paula SO (2014) Natural products as source of potential dengue antivirals. Molecules 19:8151–8176CrossRefPubMed
11.
go back to reference Lee S (2007) Artemisinin, promising lead natural product for various drug developments. Mini Rev Med Chem 7:411–422CrossRefPubMed Lee S (2007) Artemisinin, promising lead natural product for various drug developments. Mini Rev Med Chem 7:411–422CrossRefPubMed
12.
go back to reference Guantai E, Chibale K (2011) How can natural products serve as a viable source of lead compounds for the development of new/novel anti-malarials? Malar J 10:S2PubMedCentralCrossRefPubMed Guantai E, Chibale K (2011) How can natural products serve as a viable source of lead compounds for the development of new/novel anti-malarials? Malar J 10:S2PubMedCentralCrossRefPubMed
13.
go back to reference Bhakat S, Karubiu W, Jayaprakash V, Soliman ME (2014) A perspective on targeting non-structural proteins to combat neglected tropical diseases: dengue, West Nile and chikungunya viruses. Eur J Med Chem 6:677–702CrossRef Bhakat S, Karubiu W, Jayaprakash V, Soliman ME (2014) A perspective on targeting non-structural proteins to combat neglected tropical diseases: dengue, West Nile and chikungunya viruses. Eur J Med Chem 6:677–702CrossRef
14.
go back to reference Case DA, Cheatham TE, Darden T, Gohlke H, Luo R, Merz KM, Onufriev A, Simmerling C, Wang B, Woods RJ (2005) The Amber biomolecular simulation programs. J Comput Chem 26:1668–1688PubMedCentralCrossRefPubMed Case DA, Cheatham TE, Darden T, Gohlke H, Luo R, Merz KM, Onufriev A, Simmerling C, Wang B, Woods RJ (2005) The Amber biomolecular simulation programs. J Comput Chem 26:1668–1688PubMedCentralCrossRefPubMed
15.
go back to reference Nguyen PTV, Yu H, Keller PA (2014) Discovery of in silico hits targeting the nsP3 macro domain of chikungunya virus. J Mol Model 20:2216CrossRefPubMed Nguyen PTV, Yu H, Keller PA (2014) Discovery of in silico hits targeting the nsP3 macro domain of chikungunya virus. J Mol Model 20:2216CrossRefPubMed
16.
go back to reference Malet H, Coutard B, Jamal S, Dutartre H, Papageorgiou N, Neuvonen M, Ahola T, Forrester N, Gould EA, Lafitte D, Ferron F, Lescar J, Gorbalenya AE, de Lamballerie X, Canard B (2009) The crystal structures of chikungunya and Venezuelan equine encephalitis virus nsP3 Macro domains define a conserved adenosine binding pocket. J Virol 83:6534–6545PubMedCentralCrossRefPubMed Malet H, Coutard B, Jamal S, Dutartre H, Papageorgiou N, Neuvonen M, Ahola T, Forrester N, Gould EA, Lafitte D, Ferron F, Lescar J, Gorbalenya AE, de Lamballerie X, Canard B (2009) The crystal structures of chikungunya and Venezuelan equine encephalitis virus nsP3 Macro domains define a conserved adenosine binding pocket. J Virol 83:6534–6545PubMedCentralCrossRefPubMed
17.
go back to reference Voss JE, Vaney M-C, 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 468:709–712CrossRefPubMed Voss JE, Vaney M-C, 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 468:709–712CrossRefPubMed
18.
go back to reference Mann J (2002) Natural products in cancer chemotherapy: past, present and future. Nat Rev Cancer 2:143–148CrossRefPubMed Mann J (2002) Natural products in cancer chemotherapy: past, present and future. Nat Rev Cancer 2:143–148CrossRefPubMed
19.
go back to reference Mondal S, Bandyopadhyay S, Ghosh MK, Mukhopadhyay S, Roy S, Mandal C (2012) Natural products: promising resources for cancer drug discovery. Anti Cancer Agents Med Chem 12:49–75CrossRef Mondal S, Bandyopadhyay S, Ghosh MK, Mukhopadhyay S, Roy S, Mandal C (2012) Natural products: promising resources for cancer drug discovery. Anti Cancer Agents Med Chem 12:49–75CrossRef
21.
go back to reference Singh IP, Bodiwala HS (2010) Recent advances in anti-HIV natural products. Nat Prod Rep 27:1781–1800CrossRefPubMed Singh IP, Bodiwala HS (2010) Recent advances in anti-HIV natural products. Nat Prod Rep 27:1781–1800CrossRefPubMed
22.
go back to reference Bourjot M, Delang L, Van Hung N, Neyts J, Gueritte F, Leyssen P, Litaudon M (2012) Prostratin and 12-O-tetradecanoylphorbol 13-acetate are potent and selective inhibitors of chikungunya virus replication. J Nat Prod 75:2183–2187CrossRefPubMed Bourjot M, Delang L, Van Hung N, Neyts J, Gueritte F, Leyssen P, Litaudon M (2012) Prostratin and 12-O-tetradecanoylphorbol 13-acetate are potent and selective inhibitors of chikungunya virus replication. J Nat Prod 75:2183–2187CrossRefPubMed
23.
go back to reference Chowdhury IH, Koyanagi Y, Kobayashi S, Hamamoto Y, Yoshiyama H, Yoshida T, Yamamoto N (1990) The phorbol ester TPA strongly inhibits HIV-1-induced syncytia formation but enhances virus production: possible involvement of protein kinase C pathway. Virology 176:126–132CrossRefPubMed Chowdhury IH, Koyanagi Y, Kobayashi S, Hamamoto Y, Yoshiyama H, Yoshida T, Yamamoto N (1990) The phorbol ester TPA strongly inhibits HIV-1-induced syncytia formation but enhances virus production: possible involvement of protein kinase C pathway. Virology 176:126–132CrossRefPubMed
24.
go back to reference Bourjot M, Leyssen P, Eydoux C, Guillemot J-C, Canard B, Rasoanaivo P, Gueritte F, Litaudon M (2012) Chemical constituents of Anacolosa pervilleana and their antiviral activities. Fitoterapia 83:1076–1080CrossRefPubMed Bourjot M, Leyssen P, Eydoux C, Guillemot J-C, Canard B, Rasoanaivo P, Gueritte F, Litaudon M (2012) Chemical constituents of Anacolosa pervilleana and their antiviral activities. Fitoterapia 83:1076–1080CrossRefPubMed
25.
go back to reference Corlay N, Delang L, Girard-Valenciennes E, Neyts J, Clerc P, Smadja J, Gueritte F, Leyssen P, Litaudon M (2014) Tigliane diterpenes from Croton mauritianus as inhibitors of chikungunya virus replication. Fitoterapia 97:87–91CrossRefPubMed Corlay N, Delang L, Girard-Valenciennes E, Neyts J, Clerc P, Smadja J, Gueritte F, Leyssen P, Litaudon M (2014) Tigliane diterpenes from Croton mauritianus as inhibitors of chikungunya virus replication. Fitoterapia 97:87–91CrossRefPubMed
26.
go back to reference Allard P-M, Leyssen P, Martin M-T, Bourjot M, Dumontet V, Eydoux C, Guillemot J-C, Canard B, Poullain C, Gueritte F, Litaudon M (2012) Antiviral chlorinated daphnane diterpenoid orthoesters from the bark and wood of Trigonostemon cherrieri. Phytochemistry 84:160–168CrossRefPubMed Allard P-M, Leyssen P, Martin M-T, Bourjot M, Dumontet V, Eydoux C, Guillemot J-C, Canard B, Poullain C, Gueritte F, Litaudon M (2012) Antiviral chlorinated daphnane diterpenoid orthoesters from the bark and wood of Trigonostemon cherrieri. Phytochemistry 84:160–168CrossRefPubMed
27.
go back to reference Kothandan S, Swaminathan R (2014) Evaluation of in vitro antiviral activity of Vitex Negundo L., Hyptis suaveolens (L) poit., Decalepis hamiltonii Wight & Arn., to chikungunya virus. Asian Pac J Trop Dis 4(Supplement 1):S111–S115CrossRef Kothandan S, Swaminathan R (2014) Evaluation of in vitro antiviral activity of Vitex Negundo L., Hyptis suaveolens (L) poit., Decalepis hamiltonii Wight & Arn., to chikungunya virus. Asian Pac J Trop Dis 4(Supplement 1):S111–S115CrossRef
28.
go back to reference Kaur P, Thiruchelvan M, Lee RCH, Chen H, Chen KC, Ng ML, Chu JJH (2013) Inhibition of chikungunya virus replication by harringtonine, a novel antiviral that suppresses viral protein expression. Antimicrob Agents Chemother 57:155–167PubMedCentralCrossRefPubMed Kaur P, Thiruchelvan M, Lee RCH, Chen H, Chen KC, Ng ML, Chu JJH (2013) Inhibition of chikungunya virus replication by harringtonine, a novel antiviral that suppresses viral protein expression. Antimicrob Agents Chemother 57:155–167PubMedCentralCrossRefPubMed
29.
go back to reference Lucas-Hourani M, Lupan A, Despres P, Thoret S, Pamlard O, Dubois J, Guillou C, Tangy F, Vidalain P-O, Munier-Lehmann H (2013) A phenotypic assay to identify chikungunya virus inhibitors targeting the nonstructural protein nsP2. J Biomol Screen 18:172–179CrossRefPubMed Lucas-Hourani M, Lupan A, Despres P, Thoret S, Pamlard O, Dubois J, Guillou C, Tangy F, Vidalain P-O, Munier-Lehmann H (2013) A phenotypic assay to identify chikungunya virus inhibitors targeting the nonstructural protein nsP2. J Biomol Screen 18:172–179CrossRefPubMed
30.
go back to reference Pohjala L, Utt A, Varjak M, Lulla A, Merits A, Ahola T, Tammela P (2011) Inhibitors of alphavirus entry and replication identified with a stable chikungunya replicon cell line and virus-based assays. Plos One 6:e28923PubMedCentralCrossRefPubMed Pohjala L, Utt A, Varjak M, Lulla A, Merits A, Ahola T, Tammela P (2011) Inhibitors of alphavirus entry and replication identified with a stable chikungunya replicon cell line and virus-based assays. Plos One 6:e28923PubMedCentralCrossRefPubMed
31.
go back to reference Bourjot M, Leyssen P, Neyts J, Dumontet V, Litaudon M (2014) Trigocherrierin a, a potent inhibitor of chikungunya virus replication. Molecules 19:3617–3627CrossRefPubMed Bourjot M, Leyssen P, Neyts J, Dumontet V, Litaudon M (2014) Trigocherrierin a, a potent inhibitor of chikungunya virus replication. Molecules 19:3617–3627CrossRefPubMed
32.
go back to reference Nothias-Scaglia L-F, Retailleau P, Paolini J, Pannecouque C, Neyts J, Dumontet V, Roussi F, Leyssen P, Costa J, Litaudon M (2014) Jatrophane diterpenes as inhibitors of chikungunya virus replication: structure-activity relationship and discovery of a potent lead. J Nat Prod 77:1505–1512CrossRefPubMed Nothias-Scaglia L-F, Retailleau P, Paolini J, Pannecouque C, Neyts J, Dumontet V, Roussi F, Leyssen P, Costa J, Litaudon M (2014) Jatrophane diterpenes as inhibitors of chikungunya virus replication: structure-activity relationship and discovery of a potent lead. J Nat Prod 77:1505–1512CrossRefPubMed
33.
go back to reference Williamson MP, McCormick TG, Nance CL, Shearer WT (2006) Epigallocatechin gallate, the main polyphenol in green tea, binds to the T-cell receptor, CD4: potential for HIV-1 therapy. J Allergy Clin Immunol 118:1369–1374CrossRefPubMed Williamson MP, McCormick TG, Nance CL, Shearer WT (2006) Epigallocatechin gallate, the main polyphenol in green tea, binds to the T-cell receptor, CD4: potential for HIV-1 therapy. J Allergy Clin Immunol 118:1369–1374CrossRefPubMed
34.
go back to reference Chen D, Wan SB, Yang H, Yuan J, Chan TH, Dou QP (2011) EGCG, green tea polyphenols and their synthetic analogs and prodrugs for human cancer prevention and treatment, In: Makowski GS (eds) Advances in clinical chemistry, vol 53, pp 155–177 Chen D, Wan SB, Yang H, Yuan J, Chan TH, Dou QP (2011) EGCG, green tea polyphenols and their synthetic analogs and prodrugs for human cancer prevention and treatment, In: Makowski GS (eds) Advances in clinical chemistry, vol 53, pp 155–177
35.
go back to reference Sachdeva AK, Kuhad A, Chopra K (2011) Epigallocatechin gallate ameliorates behavioral and biochemical deficits in rat model of load-induced chronic fatigue syndrome. Brain Res Bull 86:165–172CrossRefPubMed Sachdeva AK, Kuhad A, Chopra K (2011) Epigallocatechin gallate ameliorates behavioral and biochemical deficits in rat model of load-induced chronic fatigue syndrome. Brain Res Bull 86:165–172CrossRefPubMed
36.
go back to reference Weber C, Sliva K, von Rhein C, Kümmerer BM, Schnierle BS The green tea catechin, epigallocatechin gallate inhibits chikungunya virus infection, Antiviral Res Weber C, Sliva K, von Rhein C, Kümmerer BM, Schnierle BS The green tea catechin, epigallocatechin gallate inhibits chikungunya virus infection, Antiviral Res
37.
go back to reference de Lamballerie X, Ninove L, Charrel RN (2009) Antiviral treatment of chikungunya virus infection. Infect Disord Drug Targets 9:101–104CrossRefPubMed de Lamballerie X, Ninove L, Charrel RN (2009) Antiviral treatment of chikungunya virus infection. Infect Disord Drug Targets 9:101–104CrossRefPubMed
Metadata
Title
Chikungunya virus (CHIKV) inhibitors from natural sources: a medicinal chemistry perspective
Authors
Soumendranath Bhakat
Mahmoud E. S. Soliman
Publication date
01-10-2015
Publisher
Springer Japan
Published in
Journal of Natural Medicines / Issue 4/2015
Print ISSN: 1340-3443
Electronic ISSN: 1861-0293
DOI
https://doi.org/10.1007/s11418-015-0910-z

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