Target specific inhibition of West Nile virus envelope glycoprotein and methyltransferase using phytocompounds: an in silico strategy leveraging molecular docking and dynamics simulation

Shopnil Akash; Imren Bayıl; Md Anisur Rahman; Nobendu Mukerjee; Swastika Maitra; Md Rezaul Islam; Sanchaita Rajkhowa; Arabinda Ghosh; Sami A Al-Hussain; Magdi E A Zaki; Vikash Jaiswal; Sanjit Sah; Joshuan J Barboza; Ranjit Sah

doi:10.3389/fmicb.2023.1189786

Target specific inhibition of West Nile virus envelope glycoprotein and methyltransferase using phytocompounds: an in silico strategy leveraging molecular docking and dynamics simulation

Front Microbiol. 2023 Jun 28:14:1189786. doi: 10.3389/fmicb.2023.1189786. eCollection 2023.

Authors

Shopnil Akash¹, Imren Bayıl², Md Anisur Rahman³, Nobendu Mukerjee^{4

5}, Swastika Maitra⁶, Md Rezaul Islam¹, Sanchaita Rajkhowa⁷, Arabinda Ghosh⁸, Sami A Al-Hussain⁹, Magdi E A Zaki⁹, Vikash Jaiswal¹⁰, Sanjit Sah^{11

12}, Joshuan J Barboza¹³, Ranjit Sah^{14

15

16}

Affiliations

¹ Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka, Bangladesh.
² Department of Bioinformatics and Computational Biology, Gaziantep University, Gaziantep, Türkiye.
³ Department of Pharmacy, Islamic University, Kushtia, Bangladesh.
⁴ Department of Microbiology, West Bengal State University, Kolkata, West Bengal, India.
⁵ Department of Health Sciences, Novel Global Community Educational Foundation, Hebersham, NSW, Australia.
⁶ Department of Microbiology, Adamas University, Kolkata, West Bengal, India.
⁷ Centre for Biotechnology and Bioinformatics, Dibrugarh University, Dibrugarh, Assam, India.
⁸ Microbiology Division, Department of Botany, Gauhati University, Gwahati, Assam, India.
⁹ Department of Chemistry, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh, Saudi Arabia.
¹⁰ Department of Cardiovascular Research, Larkin Community Hospital, South Miami, FL, United States.
¹¹ Global Consortium for Public Health and Research, Datta Meghe Institute of Higher Education and Research, Jawaharlal Nehru Medical College, Wardha, India.
¹² SR Sanjeevani Hospital, Kayanpur, Siraha, Nepal.
¹³ Escuela de Medicina, Universidad Cesar Vallejo, Trujillo, Peru.
¹⁴ Tribhuvan University Teaching Hospital, Institute of Medicine, Kathmandu, Nepal.
¹⁵ Dr. D. Y. Patil Medical College, Hospital and Research Centre, Dr. D. Y. Patil Vidyapeeth, Pune, Maharashtra, India.
¹⁶ Department of Public Health Dentistry, Dr. D.Y. Patil Dental College and Hospital, Dr. D.Y. Patil Vidyapeeth, Pune, Maharashtra, India.

Abstract

Mosquitoes are the primary vector for West Nile virus, a flavivirus. The virus's ability to infiltrate and establish itself in increasing numbers of nations has made it a persistent threat to public health worldwide. Despite the widespread occurrence of this potentially fatal disease, no effective treatment options are currently on the market. As a result, there is an immediate need for the research and development of novel pharmaceuticals. To begin, molecular docking was performed on two possible West Nile virus target proteins using a panel of twelve natural chemicals, including Apigenin, Resveratrol, Hesperetin, Fungisterol, Lucidone, Ganoderic acid, Curcumin, Kaempferol, Cholic acid, Chlorogenic acid, Pinocembrin, and Sanguinarine. West Nile virus methyltransferase (PDB ID: 2OY0) binding affinities varied from -7.4 to -8.3 kcal/mol, whereas West Nile virus envelope glycoprotein affinities ranged from -6.2 to -8.1 kcal/mol (PDB ID: 2I69). Second, substances with larger molecular weights are less likely to be unhappy with the Lipinski rule. Hence, additional research was carried out without regard to molecular weight. In addition, compounds 01, 02, 03, 05, 06, 07, 08, 09, 10 and 11 are more soluble in water than compound 04 is. Besides, based on maximum binding affinity, best three compounds (Apigenin, Curcumin, and Ganoderic Acid) has been carried out molecular dynamic simulation (MDs) at 100 ns to determine their stability. The MDs data is also reported that these mentioned molecules are highly stable. Finally, advanced principal component analysis (PCA), dynamics cross-correlation matrices (DCCM) analysis, binding free energy and dynamic cross correlation matrix (DCCM) theoretical study is also included to established mentioned phytochemical as a potential drug candidate. Research has indicated that the aforementioned natural substances may be an effective tool in the battle against the dangerous West Nile virus. This study aims to locate a bioactive natural component that might be used as a pharmaceutical.

Keywords: ADMET; PCA; West Nile virus; drug-likeness; molecular docking; molecular dynamic simulation.