Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, GA, United States of America.
PLoS One. 2021 Oct 29;16(10):e0259129. doi: 10.1371/journal.pone.0259129. eCollection 2021.
Influenza viruses cause respiratory tract infections and substantial health concerns. Infection may result in mild to severe respiratory disease associated with morbidity and some mortality. Several anti-influenza drugs are available, but these agents target viral components and are susceptible to drug resistance. There is a need for new antiviral drug strategies that include repurposing of clinically approved drugs. Drugs that target cellular machinery necessary for influenza virus replication can provide a means for inhibiting influenza virus replication. We used RNA interference screening to identify key host cell genes required for influenza replication, and then FDA-approved drugs that could be repurposed for targeting host genes. We examined the effects of Clopidogrel and Triamterene to inhibit A/WSN/33 (EC50 5.84 uM and 31.48 uM, respectively), A/CA/04/09 (EC50 6.432 uM and 3.32 uM, respectively), and B/Yamagata/16/1988 (EC50 0.28 uM and 0.11 uM, respectively) replication. Clopidogrel and Triamterene provide a druggable approach to influenza treatment across multiple strains and subtypes.
流感病毒引起呼吸道感染，对健康造成重大影响。感染可能导致轻度至重度呼吸道疾病，伴有发病率和一定的死亡率。有几种抗流感药物可用，但这些药物针对病毒成分，容易产生耐药性。因此，需要新的抗病毒药物策略，包括重新利用临床批准的药物。针对流感病毒复制所需的细胞机制的药物可以提供抑制流感病毒复制的手段。我们使用 RNA 干扰筛选来鉴定流感复制所需的关键宿主细胞基因，然后寻找可重新用于靶向宿主基因的已批准 FDA 药物。我们研究了氯吡格雷和三甲烯的作用，以抑制 A/WSN/33（EC50 分别为 5.84 μM 和 31.48 μM）、A/CA/04/09（EC50 分别为 6.432 μM 和 3.32 μM）和 B/Yamagata/16/1988（EC50 分别为 0.28 μM 和 0.11 μM）的复制。氯吡格雷和三甲烯为多种株系和亚型的流感治疗提供了一种可用药的方法。
