Allosteric inhibition of dengue virus RNA-dependent RNA polymerase by Litsea cubeba phytochemicals: a computational study

Abstract

RNA-dependent RNA polymerase (RdRp) is considered a potential drug target for dengue virus (DENV) inhibition and has attracted attention in antiviral drug discovery. Here, we screened 121 natural compounds from Litsea cubeba against DENV RdRp using various approaches of computer-based drug discovery. Notably, we identified four potential compounds (Ushinsunine, Cassameridine, (+)-Epiexcelsin, (−)-Phanostenine) with good binding scores and allosteric interactions with the target protein. Moreover, molecular dynamics simulation studies were done to check the conformational stability of the complexes under given conditions. Additionally, we performed post-simulation analysis to find the stability of potential drugs in the target protein. The findings suggest Litsea cubeba-derived phytomolecules as a therapeutic solution to control DENV infection.

Communicated by Ramaswamy H. Sarma

Keywords:

• Dengue virus
• dengue fever
• RdRp
• antiviral

Acknowledgments

The authors are highly thankful to Dr. Amaresh Kumar Sahoo, Indian Institute of Information Technology, Prayagraj, India for providing his kind support in binding free energy calculation in Prime module of Schrödinger suite.

Authors’ Contributions

Conceptualization, H.P., S.K.J., S.P.P., R.R., E.I.A., V.D.D. and A.K.J.; Data curation, H.P.; Formal analysis, H.P.; Investigation, H.P.; Methodology, H.P.; Resources, H.P.; Software, H.P. and V.D.D.; Supervision, S.K.J., E.I.A., V.D.D. and A.K.J.; Validation, H.P., S.K.J., S.P.P., R.R., E.I.A., V.D.D. and A.K.J.; Visualization, S.P.P., R.R., H.P.; Writing—original draft, H.P.; Revision: H.P., N.F.A. M.A.S., Writing—review & editing, H.P., S.K.J., M.A.S., S.P.P., N.F.A., R.R., E.I.A., V.D.D. and A.K.J.

Disclosure Statement

The authors declare no conflict of interest.

Additional information

Funding

The authors extend their appreciation to the Ministry of Education in KSA for funding the research work through the Project No. KKU-IFP2-H-26.