In silico screening of chalcones and flavonoids as potential inhibitors against yellow head virus 3C-like protease

PeerJ

article

Kanpong Boonthaworn¹  Kowit Hengphasatporn³  Yasuteru Shigeta³  Warinthorn Chavasiri⁴  Thanyada Rungrotmongkol⁵  Puey Ounjai¹ 

[1]Department of Biology, Faculty of Science, Mahidol University

[2]Center of Excellence on Environmental Health and Toxicology, Ministry of Education

[3]Center of Computational Sciences, University of Tsukuba

[4]Department of Chemistry, Faculty of Science, Center of Excellence in Natural Products Chemistry, Chulalongkorn University

[5]Structural and Computational Biology Research Unit, Department of Biochemistry, Faculty of Science, Chulalongkorn University

关键词: Yellow head virus;    3C-like protease;    Homology modeling;    Molecular docking;    Molecular dynamics simulation;   

DOI  :  10.7717/peerj.15086

学科分类：社会科学、人文和艺术（综合）

来源: Inra

【 摘 要 】

Yellow head virus (YHV) is one of the most important pathogens in prawn cultivation. The outbreak of YHV could potentially result in collapses in aquaculture industries. Although a flurry of development has been made in searching for preventive and therapeutic approaches against YHV, there is still no effective therapy available in the market. Previously, computational screening has suggested a few cancer drugs to be used as YHV protease (3CLpro) inhibitors. However, their toxic nature is still of concern. Here, we exploited various computational approaches, such as deep learning-based structural modeling, molecular docking, pharmacological prediction, and molecular dynamics simulation, to search for potential YHV 3CLpro inhibitors. A total of 272 chalcones and flavonoids were in silico screened using molecular docking. The bioavailability, toxicity, and specifically drug-likeness of hits were predicted. Among the hits, molecular dynamics simulation and trajectory analysis were performed to scrutinize the compounds with high binding affinity. Herein, the four selected compounds including chalcones cpd26, cpd31 and cpd50, and a flavonoid DN071_f could be novel potent compounds to prevent YHV and GAV propagation in shrimp. The molecular mechanism at the atomistic level is also enclosed that can be used to further antiviral development.

【 授权许可】

CC BY