Computer-Aided Structure Based Drug Design Approaches for the Discovery of New Anti-CHIKV Agents.

Surender Singh Jadav, Barij Nayan Sinha, Rolf Hilgenfeld, Venkatesan Jayaprakash
Author Information
  1. Surender Singh Jadav: Department of Pharmaceutical Sciences & Technology, Birla Insitute of Technology, Mesra, Ranchi, Jharkhand, India.
  2. Barij Nayan Sinha: Department of Pharmaceutical Sciences & Technology, Birla Insitute of Technology, Mesra, Ranchi, Jharkhand, India.
  3. Rolf Hilgenfeld: Institute of Biochemistry, Center for Structural and Cell Biology in Medicine, University of Lübeck, 23538 Lübeck, Germany.
  4. Venkatesan Jayaprakash: Department of Pharmaceutical Sciences & Technology, Birla Insitute of Technology, Mesra, Ranchi, Jharkhand, India.

Abstract

BACKGROUND: Chikungunya is a viral infection caused by Chikungunya virus (CHIKV), an arbovirus transmitted through mosquito (Aedes aegypti and Aedes albopictus) bite. The virus from sylvatic cycle in Africa mutated to new vector adaptation and became one of the major emerging and re-emerging viral infections in the past decade, affecting more than 40 countries. Efforts are being made by many researches to develop means to prevent and control the infection through vaccines and vector control strategy. On the other hand, search for novel chemotherapeutic agents for the treatment of infected patients is on. Approach of repurposed drug is one way of identifying an existing drug for the treatment of CHIKV infection.
OBJECTIVE: Review the history of CHIKV nsp2 protease inhibitors derived through structure-based computer-aided drug design along with phytochemicals identified as anti-CHIKV agents.
METHODS: A survey on CHIKV inhibitors reported till date has been carriedout. The data obtained were organized and discussed under natural substances and synthetic derivatives obtained as result of rational design.
RESULTS: The review provides a well organized content in chronological order that has highly significant information for medicinal chemist who wish to explore the area of Anti-CHIKV drug design and development. Natural compounds with different scaffolds provides an opportunity to explore Ligand based drug design (LBDD), while rational drug design approaches provides opportunity to explore the Structure based drug design.
CONCLUSION: From the presented mini-review, readers can understand that this area is less explored and has lots of potential in anti-CHIKVviral drug design & development. of reported literature inferred that, unlike other viral proteases, the nsP2 protease can be targeted for CHIKV viral inhibition. The HTVS process for the identification of anti-CHIK agents provided a few successive validated lead compounds against CHIKV infections.

Keywords

MeSH Term

Animals
Antiviral Agents
Chikungunya Fever
Chikungunya virus
Computer-Aided Design
Cysteine Endopeptidases
Drug Design
Drug Discovery
High-Throughput Screening Assays
Humans
Protease Inhibitors
Protein Kinase Inhibitors
Virus Internalization
Virus Replication

Chemicals

Antiviral Agents
Protease Inhibitors
Protein Kinase Inhibitors
Cysteine Endopeptidases
nsP2 proteinase

Word Cloud

Created with Highcharts 10.0.0drugdesignCHIKVviralChikungunyainfectionagentsproteaseinhibitorsprovidesexploreAnti-CHIKVvirusAedesvectoroneinfectionscontroltreatmentreportedobtainedorganizedrationalareadevelopmentcompoundsopportunitybasedStructurecanBACKGROUND:causedarbovirustransmittedmosquitoaegyptialbopictusbitesylvaticcycleAfricamutatednewadaptationbecamemajoremergingre-emergingpastdecadeaffecting40countriesEffortsmademanyresearchesdevelopmeanspreventvaccinesstrategyhandsearchnovelchemotherapeuticinfectedpatientsApproachrepurposedwayidentifyingexistingOBJECTIVE:Reviewhistorynsp2derivedstructure-basedcomputer-aidedalongphytochemicalsidentifiedanti-CHIKVMETHODS:surveytilldatecarriedoutdatadiscussednaturalsubstancessyntheticderivativesresultRESULTS:reviewwellcontentchronologicalorderhighlysignificantinformationmedicinalchemistwishNaturaldifferentscaffoldsLigandLBDDapproachesCONCLUSION:presentedmini-reviewreadersunderstandlessexploredlotspotentialanti-CHIKVviral&literatureinferredunlikeproteasesnsP2targetedinhibitionHTVSprocessidentificationanti-CHIKprovidedsuccessivevalidatedleadComputer-AidedBasedDrugDesignApproachesDiscoveryNewAgentsreplicationtargets

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