Potential Inhibitors of Lumpy Skin Disease's Viral Protein (DNA Polymerase): A Combination of Bioinformatics Approaches

초록

Simple Summary Lumpy skin disease (LSD) presents a formidable challenge to livestock production worldwide, spreading rapidly among ruminant animals and causing significant economic losses. Despite vaccination efforts, the limitations of existing sheep and goat pox vaccine necessitate alternative therapeutic solutions. Using computational analysis, this study focuses on identifying inhibitors that target LSDV039, a critical protein associated with LSDV. Virtual screening identifies four potent inhibitors from a library of repurposed drugs and phytocompounds, while molecular dynamics simulations validate the stability and efficacy of those selected inhibitors. Past vaccine development attempts underscore the urgency of finding more successful treatments, while the potential of repurposing drugs and phytocompounds offers hope for combating LSD. Notably, this study highlights the versatility of computational methods in drug discovery and emphasizes the need for experimental validation in order to pave the way for novel therapeutic strategies against LSD. This research offers insight into the broader potential of computational approaches in combating infectious diseases.Abstract Lumpy skin disease (LSD), caused by a virus within the Poxviridae family and Capripoxvirus genus, induces nodular skin lesions in cattle. This spreads through direct contact and insect vectors, significantly affecting global cattle farming. Despite the availability of vaccines, their efficacy is limited by poor prophylaxis and adverse effects. Our study aimed to identify the potential inhibitors targeting the LSDV-encoded DNA polymerase protein (gene LSDV039) for further investigation through comprehensive analysis and computational methods. Virtual screening revealed rhein and taxifolin as being potent binders among 380 phytocompounds, with respective affinities of -8.97 and -7.20 kcal/mol. Canagliflozin and tepotinib exhibited strong affinities (-9.86 and -8.86 kcal/mol) among 718 FDA-approved antiviral drugs. Simulating the molecular dynamics of canagliflozin, tepotinib, rhein, and taxifolin highlighted taxifolin's superior stability and binding energy. Rhein displayed compactness in RMSD and RMSF, but fluctuated in Rg and SASA, while canagliflozin demonstrated stability compared to tepotinib. This study highlights the promising potential of using repurposed drugs and phytocompounds as potential LSD therapeutics. However, extensive validation through in vitro and in vivo testing and clinical trials is crucial for their practical application.

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