Identification of Natural Terpenoid Compounds as Potential Inhibitors of Nucleoprotein of Influenza A Virus using in silico Approach: ADMET, Molecular Docking, and Molecular Dynamic Simulation

Md Saddam Hossain; Md Mosahaq Ali; Prithbay Raj; Md Parvez Khondokar; S M Jahurul Haque; Yousef A Bin Jardan; Samir Ibenmoussa; Mohammed Bourhia

doi:10.2174/0115734064311430240906112547

Identification of Natural Terpenoid Compounds as Potential Inhibitors of Nucleoprotein of Influenza A Virus using in silico Approach: ADMET, Molecular Docking, and Molecular Dynamic Simulation

Med Chem. 2025 Jan 13. doi: 10.2174/0115734064311430240906112547. Online ahead of print.

Authors

Md Saddam Hossain¹, Md Mosahaq Ali¹, Prithbay Raj², Md Parvez Khondokar¹, S M Jahurul Haque¹, Yousef A Bin Jardan³, Samir Ibenmoussa⁴, Mohammed Bourhia⁵

Affiliations

¹ Department of Biomedical Engineering, Faculty of Engineering and Technology, Islamic University, Kushtia-7003, Bangladesh.
² Department of Industrial and Production Engineering, Faculty of Mechanical Engineering, Dhaka University of Engineering and Technology, Gazipur-1707, Bangladesh.
³ Department of Pharmaceutics, College of Pharmacy, King Saud University, P.O. Box 11451, Riyadh, Saudi Arabia.
⁴ Laboratory of Therapeutic and Organic Chemistry, Faculty of Pharmacy, University of Montpellier, Montpellier 34000 France.
⁵ Laboratory of Biotechnology and Natural Resources Valorization, Faculty of Sciences of Agadir, Ibn Zohr University, Agadir, Morocco.

PMID: 39812068
DOI: 10.2174/0115734064311430240906112547

Abstract

Background: We continue to struggle with the prevention and treatment of the influenza virus. The 2009 swine flu pandemic, caused by the H1N1 strain of influenza A, resulted in numerous fatalities. The threat of influenza remains a significant concern for global health, and the development of novel drugs targeting these viruses is highly desirable.

Objective: The objective of this study is to explore the inhibitory potential of terpenoid compounds against the Nucleoprotein (NP) of influenza A virus, which is a highly effective drug target due to its ability to facilitate the transcription and replication of viral RNA.

Method: In silico research was performed to identify potential inhibitors of NP. Molecular docking studies were conducted to assess the binding of terpenoid compounds to the active site residues of the target protein. The most promising hits were then subjected to molecular dynamics simulations to examine the stability of the protein-ligand complexes. Additionally, ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) studies and Lipinski's rule of five were employed to evaluate the drug safety and druglikeness of the compounds.

Result: Docking studies revealed that the terpenoid compounds bind strongly to the active site residues of the NP protein. Molecular dynamics simulations demonstrated the stability of the proteinligand complexes for the best-hit compounds. ADMET studies and Lipinski's filter indicated that the compounds exhibit desirable drug safety and drug-likeness profiles.

Conclusion: This work may contribute significantly to drug discovery and the development of therapeutic agents against the influenza A virus. The identification of terpenoid compounds that bind strongly to the NP protein and exhibit favorable drug-like properties through in silico studies provides a promising foundation for further research and the development of potential inhibitors targeting this critical viral protein.

Keywords: ADMET; MD simulations.; Terpenoid; influenza A; molecular docking; nucleoprotein.