In silico identification of natural antiviral compounds as a potential inhibitor of chikungunya virus non-structural protein 3 macrodomain

Abstract

Chikungunya Virus (CHIKV) is having a major impact on humans with potentially life-threatening and debilitating arthritis. The lack of a specific antiviral drug against the CHIKV disease has created an alarming situation to identify or develop potent chemical molecules for its remedial measures. Antiviral therapies for viral diseases are generally expensive and have adverse side effects. Plant-based antiviral natural compounds are the most suitable and best alternative of current antiviral drugs because of less toxicity. In the present study, non-structural protein 3 macrodomain (nsP3^MD) of the CHIKV that is essential for virus replication has been selected for anti CHIKV drug target. The compounds were identified using molecular docking, virtual screening and further evaluated by molecular dynamics (MD) simulation studies. The binding mechanism of each compound was analyzed considering the stability and energetic parameter. We have found six plant-based natural antiviral compounds Baicalin, Rutaecarpine, Amentoflavone, Apigetrin, Luteoloside, and Baloxavir as strong inhibitors of nsP3^MD of CHIKV. ADMET prediction and target analysis of the selected compounds showed drug likeliness of these compounds. MD simulation studies indicated energetically favorable complex formation between nsP3^MD and the selected antiviral compounds. Furthermore, the structural effects on these substitutions were analyzed using the principles of each trajectory, which validated the interaction studies. Our analysis suggests a very high probability of these compounds to inhibit nsP3^MD of CHIKV and could be evaluated for Chikungunya fever drug development.

Communicated by Ramaswamy H. Sarma

Keywords:

• Absorption
• distribution
• metabolism
• excretion and toxicity
• ADP-ribose
• Chikungunya virus
• non-structural protein 3
• structure-based virtual screening

Disclosure statement

The authors declare that there are no conflicts of interest.

Additional information

Funding

This work was supported by the Government of India Ministry of Sciences and Technology, Department of Science and Technology, under the DST (WOS-A) Grant number: [SR/WOS-A/LS-110/2018(G)] to M.C. The authors would also like to thank Shiv Nadar University, a providing lab infrastructure to carry out this work.