Ligand-based drug design against Herpes Simplex Virus-1 capsid protein by modification of limonene through in silico approaches.

Autor: Islam MR; Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka, Bangladesh, 1207., Islam Sovon MS; Department of Pharmacy, Faculty of Pharmacy, University of Dhaka, Dhaka, 1000, Bangladesh., Amena U; Department of Pharmacy, Faculty of Life & Earth Sciences, Jagannath University, Dhaka, Bangladesh., Rahman M; Department of Pharmaceutical Sciences, North South University, Dhaka, 1219, Bangladesh., Hosen ME; Department of Genetic Engineering and Biotechnology, University of Rajshahi, Rajshahi, 6205, Bangladesh., Kumer A; Department of Chemistry, College of Arts and Sciences, International University of Business Agriculture and Technology (IUBAT), Dhaka, 1216, Bangladesh.; Center for Global Health Research, Saveetha Institute of Medical and Technical Sciences in Saveetha Medical College and Hospital, Chennai, India., Bourhia M; Laboratory of Biotechnology and Natural Resources Valorization, Faculty of Sciences, Ibn Zohr University, 80060, Agadir, Morocco. bourhiamohammed@gmail.com., Bin Jardan YA; Department of Pharmaceutics, College of Pharmacy, King Saud University, P.O. Box 11451, Riyadh, Saudi Arabia., Ibenmoussa S; Laboratory of Therapeutic and Organic Chemistry, Faculty of Pharmacy, University of Montpellier, 34000, Montpellier, France., Wondmie GF; Department of Biology, Bahir Dar University, P.O. Box 79, Bahir Dar, Ethiopia. resercherfent@gmail.com.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2024 Apr 29; Vol. 14 (1), pp. 9828. Date of Electronic Publication: 2024 Apr 29.
DOI: 10.1038/s41598-024-59577-4
Abstrakt: The pharmacological effects of limonene, especially their derivatives, are currently at the forefront of research for drug development and discovery as well and structure-based drug design using huge chemical libraries are already widespread in the early stages of therapeutic and drug development. Here, various limonene derivatives are studied computationally for their potential utilization against the capsid protein of Herpes Simplex Virus-1. Firstly, limonene derivatives were designed by structural modification followed by conducting a molecular docking experiment against the capsid protein of Herpes Simplex Virus-1. In this research, the obtained molecular docking score exhibited better efficiency against the capsid protein of Herpes Simplex Virus-1 and hence we conducted further in silico investigation including molecular dynamic simulation, quantum calculation, and ADMET analysis. Molecular docking experiment has documented that Ligands 02 and 03 had much better binding affinities (- 7.4 kcal/mol and - 7.1 kcal/mol) to capsid protein of Herpes Simplex Virus-1 than Standard Acyclovir (- 6.5 kcal/mol). Upon further investigation, the binding affinities of primary limonene were observed to be slightly poor. But including the various functional groups also increases the affinities and capacity to prevent viral infection of the capsid protein of Herpes Simplex Virus-1. Then, the molecular dynamic simulation confirmed that the mentioned ligands might be stable during the formation of drug-protein complexes. Finally, the analysis of ADMET was essential in establishing them as safe and human-useable prospective chemicals. According to the present findings, limonene derivatives might be a promising candidate against the capsid protein of Herpes Simplex Virus-1 which ultimately inhibits Herpes Simplex Virus-induced encephalitis that causes interventions in brain inflammation. Our findings suggested further experimental screening to determine their practical value and utility.
(© 2024. The Author(s).)
Databáze: MEDLINE
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