Natural compounds inhibit Monkeypox virus methyltransferase VP39 in silico studies

Abstract

VP39, an essential 2′-O-RNA methyltransferase enzyme discovered in Monkeypox virus (MPXV), plays a vital role in viral RNA replication and transcription. Inhibition of the enzyme may prevent viral replication. In this context, using a combination of molecular docking and molecular dynamics (MDs) simulations, the inhibitory ability of NCI Diversity Set VII natural compounds to VP39 protein was investigated. It should be noted that the computed binding free energy of ligand via molecular docking and linear interaction energy (LIE) approaches are in good agreement with the corresponding experiments with coefficients of $R=0.72$ and 0.75, respectively. NSC 319990, NSC 196515 and NSC 376254 compounds were demonstrated that can inhibit MPVX methyltransferase VP39 protein with the similar affinity compared to available inhibitor sinefungin. Moreover, nine residues involving Gln39, Gly68, Gly72, Asp95, Arg97, Val116, Asp138, Arg140 and Asn156 may be argued that they play an important role in binding process of inhibitors to VP39.

Communicated by Ramaswamy H. Sarma

Keywords:

• MPVX
• VP39
• LIE
• docking
• NCI

Disclosure statement

The authors declare that there is no conflict of interest.

Author contributions

Conceptualization: HTTP and LHT; Data curation: THL and LHT; Formal analysis: THL; Methodology: THL and LHT; Resources: LHT; Supervision: HTTP; Validation: LHT and HTTP; Visualization: THL; Roles/Writing – original draft: HTTP; Writing – review and editing: THL, LHT and HTTP.

QMT: Investigation, Formal analysis and Validation; HTTP: Writing – Original Draft; NQAP and JTH: Supervision; PTT: Funding acquisition, Supervision; NTT: Resources, Supervision; STN: Conceptualization, Methodology, Validation, Writing – Original Draft, Funding acquisition and Project administration.

Additional information

Funding

This work was supported by funded by Vingroup Innovation Foundation (VINIF) under project code VINIF.2022.DA00061 and Ho Chi Minh City Foundation for Science and Technology Development under grant number 115/QĐ-SKHCN.