title: Computer-Aided Structure Based Drug Design Approaches for the Discovery of New Anti-CHIKV Agents.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pharmaceutical Sciences & Technology, Birla Insitute of Technology, Mesra, Ranchi, Jharkhand, India.
authors.forename: Surender Singh
authors.initials: SS
authors.lastname: Jadav
authors.affiliation: Department of Pharmaceutical Sciences & Technology, Birla Insitute of Technology, Mesra, Ranchi, Jharkhand, India.
authors.forename: Barij Nayan
authors.initials: BN
authors.lastname: Sinha
authors.affiliation: Institute of Biochemistry, Center for Structural and Cell Biology in Medicine, University of Lübeck, 23538 Lübeck, Germany.|German Center for Infection Research (DZIF), Lübeck, Germany.
authors.forename: Rolf
authors.initials: R
authors.lastname: Hilgenfeld
authors.affiliation: Department of Pharmaceutical Sciences & Technology, Birla Insitute of Technology, Mesra, Ranchi, Jharkhand, India.
authors.forename: Venkatesan
authors.initials: V
authors.lastname: Jayaprakash
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry* / Q000494:pharmacology*; D065632:Chikungunya Fever / Q000188:drug therapy* / Q000201:enzymology / Q000635:transmission; D002646:Chikungunya virus / Q000187:drug effects* / Q000502:physiology; D017076:Computer-Aided Design; D003546:Cysteine Endopeptidases / Q000378:metabolism; D015195:Drug Design; D055808:Drug Discovery / Q000379:methods*; D057166:High-Throughput Screening Assays / Q000379:methods; D006801:Humans; D011480:Protease Inhibitors / Q000737:chemistry / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000494:pharmacology; D053586:Virus Internalization / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D011480:Protease Inhibitors; D047428:Protein Kinase Inhibitors; D003546:Cysteine Endopeptidases; C078306:nsP2 proteinase
keywords: Anti-CHIKV; Chikungunya; drug design; inhibitors; protease.; replication; targets