High-throughput screening of natural antiviral drug candidates against white spot syndrome virus targeting VP28 in Penaeus monodon: Computational drug design approaches
IF 3.5 Q3 Biochemistry, Genetics and Molecular Biology
Md. Touki Tahamid Tusar , Zubaer Hossen , Hafizur Rahman Gazi , Niamul Haq , Abdullah-Al Jubayer , Md Mahmudul Islam , Asura Khanam Lisa , Biswanath Sikdar , Md. Enamul Haque
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引用次数: 0
Abstract
The white spot syndrome virus (WSSV), considered the deadliest pathogen impacting Penaeid shrimp (Penaeus monodon), remains worrisome for the global shrimp industry due to its extreme virulence and mortality rate of up to 100%. To date, there has been no breakthrough in effective antivirals or vaccines that can mitigate the financial damage caused by the pathogen. The distinctive structure of VP28 facilitates its role as a trimer, serving as the primary envelope protein of WSSV. It anchors to the viral envelope, directly interacts with PmRab7, a membrane protein in P. monodon, and aids in entry into the host. This research aims to discover antiviral drug candidates targeting VP28 trimer by screening a virtual library of 187 bioactive compounds derived from the medicinal herbs Azadirachta indica and Bacopa monnieri. To evaluate the drug ability of compounds in restricting VP28 trimer interaction within the endocytic pathway, a computational strategy was employed, including virtual screening, pharmacokinetics and toxicity analysis, and molecular dynamics (MD) simulation. The four strongest compounds, epicatechin, luteolin, kaempferol, and apigenin, exhibited binding affinities of −8.8, −8.8, −8.7, and −8.5 Kcal/mol, respectively, and demonstrated excellent pharmacokinetic properties. Furthermore, we employed 100 nanoseconds MD simulations and MM-PBSA binding free energy calculations to examine intermolecular interactions and confirmed the structural stability of the compounds at the VP28 binding site. The findings of this research suggest that these compounds hold promise in combating WSSV infection, reducing economic losses, and contributing to the sustainability of the shrimp industry.
期刊介绍:
Journal of genetic engineering and biotechnology is devoted to rapid publication of full-length research papers that leads to significant contribution in advancing knowledge in genetic engineering and biotechnology and provide novel perspectives in this research area. JGEB includes all major themes related to genetic engineering and recombinant DNA. The area of interest of JGEB includes but not restricted to: •Plant genetics •Animal genetics •Bacterial enzymes •Agricultural Biotechnology, •Biochemistry, •Biophysics, •Bioinformatics, •Environmental Biotechnology, •Industrial Biotechnology, •Microbial biotechnology, •Medical Biotechnology, •Bioenergy, Biosafety, •Biosecurity, •Bioethics, •GMOS, •Genomic, •Proteomic JGEB accepts