Weiqi Zhao, Mengqi Zhao, Fuhui Chang, Yihan Yuan, Qinghua Geng, Shouhua Feng, Gen Lu, Kang Ou, Xiaoyue Chen, Shu Wei, Zuofeng Yang, Jinling Liu
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引用次数: 0
Abstract
Objective: African swine fever is a devastating swine disease lacking effective vaccines or antiviral drugs. The African swine fever virus (ASFV) pE165R deoxyuridine triphosphatase (dUTPase), critical for viral replication, is a promising antiviral target. Therefore, identifying inhibitors that target the pE165R protein represents a potential antiviral strategy.
Methods: The study computationally screened FDA-approved drugs against pE165R's crystal structure. Molecular dynamics simulations elucidated inhibitor-pE165R interactions, and in vitro enzymatic assays quantitatively assessed inhibitory effects.
Results: 4 candidates predominantly targeted pE165R's active pocket (Serine-72, Arginine-71, and Serine-73), suggesting competitive inhibition, with strong binding free energies (up to -40.5 kcal/mol) observed by molecular mechanics/Poisson-Boltzmann surface area.
Conclusions: In vitro assays confirmed dideoxyinosine triphosphate (77.9%) potently inhibited pE165R activity at 0.1mM.
Clinical relevance: Effective drugs against ASFV remain lacking. Based on a drug-repurposing strategy, this study screened the FDA-approved drug library for compounds targeting pE165R, a key protein involved in ASFV replication. Subsequent pharmacodynamic evaluation is expected to facilitate the identification of affordable and effective anti-ASFV therapeutics for clinical application, thereby providing a theoretical foundation for the effective prevention and control of African swine fever.
期刊介绍：
The American Journal of Veterinary Research supports the collaborative exchange of information between researchers and clinicians by publishing novel research findings that bridge the gulf between basic research and clinical practice or that help to translate laboratory research and preclinical studies to the development of clinical trials and clinical practice. The journal welcomes submission of high-quality original studies and review articles in a wide range of scientific fields, including anatomy, anesthesiology, animal welfare, behavior, epidemiology, genetics, heredity, infectious disease, molecular biology, oncology, pharmacology, pathogenic mechanisms, physiology, surgery, theriogenology, toxicology, and vaccinology. Species of interest include production animals, companion animals, equids, exotic animals, birds, reptiles, and wild and marine animals. Reports of laboratory animal studies and studies involving the use of animals as experimental models of human diseases are considered only when the study results are of demonstrable benefit to the species used in the research or to another species of veterinary interest. Other fields of interest or animals species are not necessarily excluded from consideration, but such reports must focus on novel research findings. Submitted papers must make an original and substantial contribution to the veterinary medicine knowledge base; preliminary studies are not appropriate.
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