Department of Medical, Surgical and Experimental Sciences, University of Sassari, 07100 Sassari, Italy.
Department of Biomedical Sciences, Cittadella Universitaria Monserrato, University of Cagliari, 09042 Monserrato, Italy.
Viruses. 2022 Jun 14;14(6):1300. doi: 10.3390/v14061300.
Bovine viral diarrhea virus (BVDV), also known as Pestivirus A, causes severe infection mostly in cattle, but also in pigs, sheep and goats, causing huge economical losses on agricultural farms every year. The infections are actually controlled by isolation of persistently infected animals and vaccination, but no antivirals are currently available to control the spread of BVDV on farms. BVDV binds the host cell using envelope protein E2, which has only recently been targeted in the research of a potent and efficient antiviral. In contrast, RdRp has been successfully inhibited by several classes of compounds in the last few decades. As a part of an enduring antiviral research agenda, we designed a new series of derivatives that emerged from an isosteric substitution of the main scaffold in previously reported anti-BVDV compounds. Here, the new compounds were characterized and tested, where several turned out to be potent and selectively active against BVDV. The mechanism of action was thoroughly studied using a time-of-drug-addition assay and the results were validated using docking simulations.
牛病毒性腹泻病毒（BVDV），也称为瘟病毒 A，主要感染牛，但也感染猪、绵羊和山羊，每年在农业养殖场造成巨大的经济损失。这些感染实际上通过隔离持续性感染动物和疫苗接种来控制，但目前没有抗病毒药物可用于控制 BVDV 在农场的传播。BVDV 使用包膜蛋白 E2 结合宿主细胞，该蛋白最近才成为研究强效和有效的抗病毒药物的目标。相比之下，RdRp 在过去几十年中已被几类化合物成功抑制。作为持久抗病毒研究议程的一部分，我们设计了一系列新的衍生物，这些衍生物是从以前报道的抗 BVDV 化合物的主要支架的等排取代中产生的。在这里，对新化合物进行了表征和测试，其中一些对 BVDV 表现出很强的选择性和活性。使用加药时间测定法彻底研究了作用机制，并使用对接模拟验证了结果。
