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.

中文翻译：

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块状皮肤病病毒蛋白（DNA 聚合酶）的潜在抑制剂：生物信息学方法的组合

肿块性皮肤病（LSD）是由痘病毒科和山羊痘病毒属的病毒引起的，会引起牛的结节性皮肤病变。这种疾病通过直接接触和昆虫媒介传播，严重影响全球养牛业。尽管有疫苗，但其功效因预防效果差和不良反应而受到限制。我们的研究旨在确定针对 LSDV 编码的 DNA 聚合酶蛋白（基因 LSDV039）的潜在抑制剂，以便通过综合分析和计算方法进行进一步研究。虚拟筛选显示大黄酸和花旗松素是 380 种植物化合物中的有效结合剂，其亲和力分别为 -8.97 和 -7.20 kcal/mol。在 FDA 批准的 718 种抗病毒药物中，卡格列净和替泊替尼表现出很强的亲和力（-9.86 和 -8.86 kcal/mol）。对卡格列净、替泊替尼、大黄酸和花旗松素的分子动力学进行模拟，突显了花旗松素的卓越稳定性和结合能。大黄酸在 RMSD 和 RMSF 中表现出致密性，但在 Rg 和 SASA 中表现出波动，而卡格列净与替泊替尼相比表现出稳定性。这项研究强调了使用重新利用的药物和植物化合物作为潜在的 LSD 疗法的巨大潜力。然而，通过体外和体内测试以及临床试验进行的广泛验证对于其实际应用至关重要。