Drug Repurposing: A Potential Therapeutic Strategy for the Treatment of Chikugunya Virus

Abstract

Abstract Chikungunya virus (CHIKV) infection is one of the major public health concerns in several countries around the world. CHIKV non-structural protein 2 (nsP2) is a promising drug design target due to the enzymes multifunctional properties that facilities viral replication and propagation. To date, there is an evident lack of preventative and therapeutic developments that can be used against CHIKV. Drug repurposing is a time saving and cost-effective method used for the development of new drugs. In this study, drug repurposing was implemented with the use of HIV/HCV protease inhibitors to inhibit the active site of nsP2. Molecular dynamics simulations and analysis revealed the stability of two drugs, Indinavir and Paritaprevir. Indinavir forms a hydrogen bond with a major residue, which closes the flexible loop, situated in close proximity to the active site. This conformational shift in the orientation of the enzyme prevents accessibility to the active site thus disrupting the nsP2 protein from functioning effectively in viral replication. In conclusion, the findings of this study identified Indinavir was identified as a promising CHIKV nsP2 inhibitor. This study will provide the basis to further facilitate the drug repurposing strategy as an alternative approach for drug design of CHIKV inhibitors as well as other viral families.