Mayo Clinic, Department of Infectious Diseases, Rochester, MN, 55905, USA.
Mayo Clinic, Department of Infectious Diseases, Rochester, MN, 55905, USA; Mayo Clinic, Department of Molecular Medicine, Rochester, MN, 55905, USA.
Antiviral Res. 2022 Apr;200:105291. doi: 10.1016/j.antiviral.2022.105291. Epub 2022 Mar 13.
Bourbon virus (BRBV) is an emerging tick-borne orthomyxovirus that causes severe febrile illness in humans. There are no specific treatments for BRBV disease currently available. Here, we developed a highly accessible and robust, quantitative fluorescence-based BRBV minigenome (MG) system and applied it to high-throughput antiviral drug screening. We demonstrated that human dihydroorotate dehydrogenase (DHODH) inhibitors, hDHODH-IN-4 and brequinar, efficiently reduced BRBV RNA synthesis, and validated these findings using infectious BRBV in vitro. The DHODH inhibitors also exhibited high potency in inhibiting MG activities of other orthomyxoviruses with emerging zoonotic potential, including bat influenza A virus, swine influenza D virus, and Thogoto virus. Our newly developed MG system is a powerful platform for antiviral drug screening across the Orthomyxoviridae family, enabling rapid development and deployment of antivirals against future emerging orthomyxoviruses.
波邦病毒（BRBV）是一种新兴的蜱传正粘病毒，可导致人类严重的发热疾病。目前尚无针对 BRBV 疾病的特效治疗方法。在这里，我们开发了一种高度可及且强大的基于荧光的 BRBV 小基因组（MG）系统，并将其应用于高通量抗病毒药物筛选。我们证明了人二氢乳清酸脱氢酶（DHODH）抑制剂 hDHODH-IN-4 和布雷奎纳能够有效抑制 BRBV RNA 合成，并通过体外感染 BRBV 验证了这些发现。DHODH 抑制剂对具有新兴人畜共患潜力的其他正粘病毒（包括蝙蝠流感 A 病毒、猪流感 D 病毒和 Thogoto 病毒）的 MG 活性也具有高抑制活性。我们新开发的 MG 系统是一种用于抗 Orthomyxoviridae 家族中抗病毒药物筛选的强大平台，能够快速开发和部署针对未来新兴正粘病毒的抗病毒药物。
