Bovine viral diarrhea virus (BVDV) infection is still a plague that causes important livestock pandemics. Despite the availability of vaccines against BVDV, and the implementation of massive eradication or control programs, this virus still constitutes a serious agronomic burden. Therefore, the alternative approach to combat Pestivirus infections, based on the development of antiviral agents that specifically inhibit the replication of these viruses, is of preeminent actuality and importance.

Capitalizing from a long-standing experience in antiviral drug design and development, in this work we present and characterize a series of small molecules based on the 9-aminoacridine scaffold that exhibit potent anti-BVDV activity coupled with low cytotoxicity. The relevant viral protein target – the RNA-dependent RNA polymerase – the binding mode, and the mechanism of action of these new antivirals have been determined by a combination of in vitro (i.e., enzymatic inhibition, isothermal titration calorimetry and site-directed mutagenesis assays) and computational experiments. The overall results obtained confirm that these acridine-based derivatives are promising compounds in the treatment of BVDV infections and, based on the reported structure-activity relationship, can be selected as a starting point for the design of a new generation of improved, safe and selective anti-BVDV agents.

牛病毒性腹泻病毒（BVDV）感染仍然是引起重要牲畜大流行的瘟疫。尽管可获得针对BVDV的疫苗，并且已经实施了大规模的根除或控制计划，但这种病毒仍然构成了严重的农业负担。因此，基于抗病毒药的发展来对抗瘟病毒感染的替代方法具有特殊的现实性和重要性，该抗病毒剂可以特异性抑制这些病毒的复制。

利用在抗病毒药物设计和开发方面的长期经验，在这项工作中，我们介绍并表征了一系列基于9-氨基ac啶骨架的小分子，这些小分子表现出强大的抗BVDV活性以及低细胞毒性。相关的病毒蛋白靶标-RNA依赖的RNA聚合酶-结合方式以及这些新抗病毒药的作用机理已通过体外联合测定（即酶促抑制，等温滴定量热法和定点诱变分析）和计算实验。获得的总体结果证实，这些基于a啶的衍生物是治疗BVDV感染的有前途的化合物，并且根据报道的结构-活性关系，可以将其作为设计新一代改良，安全和高效的起点。选择性抗BVDV剂。