Molecular modelling and simulation techniques to investigate the effects of fungal metabolites on the SARS-CoV-2 RdRp protein inhibition

Journal of King Saud University: Science

Veeranna S. Hombalimath¹  Fahad Alsaikhan¹  Basheerahmed Abdulaziz Mannasaheb²  Saleh A. Alshamrani³  Amal Bahafi⁴  Aejaz Abdul Latif Khan⁵  Shrikanth Badiger⁶  Uday M. Muddapur⁶  Mater H. Mahnashi⁷  Rasha Hamed Al-Serwi⁸  S.M. Shakeel Iqubal⁹  Tasneem Mohammed⁹  Mohamed El-Sherbiny^1,10  Helen Suban Mohammed Gouse^1,11  Mohammed M. Ghoneim^1,12  Ibrahim Ahmed Shaikh^1,13  Touseef Begum^1,14 

[1]Corresponding authors at: Department of General Science, Ibn Sina National College for Medical Studies, Al Mahajar Street: 31906, Jeddah 21418, Saudi Arabia (S.M.S. Iqubal).

[2]Department of Anatomy, Faculty of Medicine, Mansoura University, Mansoura, Egypt

[3]Department of Pharmacy Practice, College of Pharmacy, AlMaarefa University, Dariyah, 13713 Riyadh, Saudi Arabia

[4]Department of Basic Dental Sciences, College of Dentistry, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia

[5]Department of Basic Medical Sciences, College of Medicine, AlMaarefa University, P.O. Box 71666, Riyadh 11597, Saudi Arabia

[6]Department of Biotechnology, KLE Technological University, BVB Campus, Hubballi 580031, Karnataka, India

[7]Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Najran University, Najran, Saudi Arabia

[8]Department of Clinical Pharmacy, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Alkharj 11942, Saudi Arabia

[9]Department of General Science, Ibn Sina National College for Medical Studies, Jeddah, Saudi Arabia

[10]Department of Pharmaceutical Chemistry, College of Pharmacy, Najran University, Najran, Saudi Arabia

[11]Department of Pharmaceutical Sciences, Ibn Sina National College for Medical Studies, Jeddah, Saudi Arabia

[12]Department of Pharmacognosy and Medicinal Plants, Faculty of Pharmacy, Al-Azhar University, Cairo 11884, Egypt

[13]Department of Pharmacology, College of Pharmacy, Najran University, Najran, Saudi Arabia

[14]Department of Pharmacy Practice, College of Pharmacy, AlMaarefa University, Dariyah, 13713 Riyadh, Saudi Arabia

关键词: SARS-CoV-2;    RdRp;    Insilico molecular docking analysis;    Molecular dynamics simulation;    ADMET analysis;    Fungal metabolites;   

DOI  :  

来源: DOAJ

【 摘 要 】

Various protein/receptor targets have been discovered through in-silico research. They are expanding rapidly due to their extensive advantage of delivering new drug candidates more quickly, efficiently, and at a lower cost. The automation of organic synthesis and biochemical screening will lead to a revolution in the entire research arena in drug discovery. In this research article, a few fungal metabolites were examined through an in-silico approach which involves major steps such as (a) Molecular Docking Analysis, (b) Drug likeness and ADMET studies, and (c) Molecular Dynamics Simulation. Fungal metabolites were taken from Antibiotic Database which showed antiviral effects on severe viral diseases such as HIV. Docking, Lipinski's, and ADMET analyses investigated the binding affinity and toxicity of five metabolites: Chromophilone I, iso; F13459; Stachyflin, acetyl; A-108836; Integracide A (A-108835). Chromophilone I, iso was subjected to additional analysis, including a 50 ns MD simulation of the protein to assess the occurring alterations. This molecule's docking data shows that it had the highest binding affinity. ADMET research revealed that the ligand might be employed as an oral medication. MD simulation revealed that the ligand–protein interaction was stable. Finally, this ligand can be exploited to develop SARS-CoV-2 therapeutic options. Fungal metabolites that have been studied could be a potential source for future lead candidates. Further study of these molecules may result in creating an antiviral drug to battle the SARS-CoV-2 virus.

【 授权许可】

Unknown