Identification of potential inhibitors targeting Ebola virus VP35 protein: a computational strategy

Abstract

Ebola virus (EBOV) poses a severe threat as a highly infectious pathogen, causing devastating hemorrhagic fever in both humans and animals. The EBOV virus VP35 protein plays a crucial role in viral replication and exhibits the ability to suppress the host interferon cascade, leading to immune system depletion. As a potential drug target, VP35 protein inhibition holds promise for combating EBOV. To discover new drug candidates, we employed a computer-aided drug design approach, focusing on compounds capable of inhibiting VP35 protein replication. In this connection, a pharmacophore model was generated using molecular interactions between the VP35 protein and its inhibitor. ZINC and Cambridge database were screened using validated pharmacophore model. Further the compounds were filtered based on Lipinski’s rule of five and subjected to MD simulation and relative binding free energy calculation. Six compounds manifest a significant docking score and strong binding interaction towards VP35 protein. MD simulations further confirmed the remarkable stability of these six complexes. Relative binding free energy calculations also showed significant ΔG value in the range of −132.3 and −49.3 kcal/mol. This study paves the way for further optimization of these compounds as potential inhibitors of VP35, facilitating subsequent experimental in vitro studies.

Communicated by Ramaswamy H. Sarma

Keywords:

• Ebola virus
• virtual screening
• molecular docking simulation
• pharmacophore
• in silico

Acknowledgement

The authors extend their appreciation to the Deanship of Scientific Research at King Khalid University for funding this work through Large Group Research Project under grant number RGP1/132/44.

Disclosure statement

No potential conflict of interest was reported by the authors.

Author contributions

Yan-kun Chen: Conceptualization, Methodology, Validation and Writing—original draft. Reem M. Gahtani: Formal analysis and Validation. Mesfer Al Shahrani: Formal anaysis and Validation. Umme Hani: Funding acquisition, and Review & editing. Fahad M. Alshabrmi: Sarfaraz Alam: Conceptualization and Methodology. Hailah M. Almohaimeed: Methodology, Validation and Writing—review & editing. Ammar A. Basabrain: Methodology, Validation and Writing—review & editing. Muhammad Shahab: Conceptualization, Methodology, Validation and Writing—review & editing. and Meng-Zhou Xie: Funding acquisition, and Review & editing. All authors have read and agreed to the published version of the manuscript.

Additional information

Funding

The research was supported by Hunan Provincial Key R & D Plan (Grant No. 2022SK2018), Hunan Graduate Research Innovation Project (No. CX20210685), Open Project of Key Laboratory of Agricultural Product Processing and Storage of Ministry of Agriculture and Rural Affairs, Key laboratory of the Quality and Safety Collection and Transportation Management and Control of Ministry of Agriculture and Rural Affairs (No. S2022KFKT-09).