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.