Exploring potential inhibitors against Kyasanur forest disease by utilizing molecular dynamics simulations and ensemble docking

Abstract

Kyasanur forest disease (KFD) is a tick-borne, neglected tropical disease, caused by KFD virus (KFDV) which belongs to Flavivirus (Flaviviridae family). This emerging viral disease is a major threat to humans. Currently, vaccination is the only controlling method against the KFDV, and its effectiveness is very low. An effective control strategy is required to combat this emerging tropical disease using the existing resources. In this regard, in silico drug repurposing method offers an effective strategy to find suitable antiviral drugs against KFDV proteins. Drug repurposing is an effective strategy to identify new use for approved or investigational drugs that are outside the scope of their initial usage and the repurposed drugs have lower risk and higher safety compared to de novo developed drugs, because their toxicity and safety issues are profoundly investigated during the preclinical trials in human/other models. In the present work, we evaluated the effectiveness of the FDA approved and natural compounds against KFDV proteins using in silico molecular docking and molecular simulations. At present, no experimentally solved 3D structures for the KFD viral proteins are available in Protein Data Bank and hence their homology model was developed and used for the analysis. The present analysis successfully developed the reliable homology model of NS3 of KFDV, in terms of geometry and energy contour. Further, in silico molecular docking and molecular dynamics simulations successfully presented four FDA approved drugs and one natural compound against the NS3 homology model of KFDV.

Communicated by Ramaswamy H. Sarma

Graphical Abstract

Keywords:

• Kyasanur forest disease
• NS3
• molecular dynamics
• Aspertryptanthrin C
• Grazoprevir

Acknowledgment

S.K, J.N., M.A.G, and V.A.P, acknowledges the Ministry of Science and Higher Education of Russia (Grant FENU-2020-0019).

Disclosure statement

The authors declare no conflict of interest.

Author contributions

S.K and B.K. devised the project, the main conceptual ideas and proof outline; S.K., S.B.S and J.N. conducted the computational studies; S.K., J.N. and B.K. wrote the manuscript, M.A.G. and V.A.P. conducted complementary principle analysis; S.K., J.N. and B.K. edited and approved the final version of manuscript. All authors have read and agreed to the published version of the manuscript.