Bovine viral diarrhea virus (BVDV) is a pestivirus whose infection in cattle is globally distributed. The use of antivirals could complement vaccination as a tool of control and reduce economic losses. The RNA-dependent RNA polymerase (RdRp) of the virus is essential for its genome replication and constitutes an attractive target for the identification of antivirals. With the aim of obtaining selective BVDV inhibitors, the crystal structure of BVDV RdRp was used to perform a virtual screening. Approximately 15,000 small molecules from commercial and in-house databases were evaluated and several structurally different compounds were tested in vitro for antiviral activity. Interestingly, of twelve evaluated compounds, five were active and displayed EC₅₀ values in the sub and low-micromolar range. Time of drug addition experiment and measured intracellular BVDV RNA showed that compound 7 act during RNA synthesis. Molecular Dynamics and MM/PBSA calculation were done to characterize the interaction of the most active compounds with RdRp, which will allow future ligand optimization. These studies highlight the use of in silico screening to identify a new class of BVDV inhibitors.

牛病毒性腹泻病毒（BVDV）是一种瘟病毒，其在牛中的感染在全球范围内分布。抗病毒药的使用可以补充疫苗接种作为控制手段，并减少经济损失。病毒的RNA依赖性RNA聚合酶（RdRp）对于其基因组复制是必不可少的，并且构成了抗病毒药物鉴定的诱人靶标。为了获得选择性的BVDV抑制剂，使用BVDV RdRp的晶体结构进行虚拟筛选。对来自商业数据库和内部数据库的大约15,000个小分子进行了评估，并在体外测试了几种结构不同的化合物的抗病毒活性。有趣的是，在十二种被评估化合物中，有五种处于活性状态并显示出EC ₅₀值在亚微摩尔和低微摩尔范围内。药物添加实验和测量细胞内BVDV RNA的时间表明，化合物7在RNA合成过程中起作用。进行了分子动力学和MM / PBSA计算以表征最具活性的化合物与RdRp的相互作用，这将使将来的配体优化成为可能。这些研究突出了计算机筛选技术的使用，以鉴定一类新的BVDV抑制剂。