Laboratory of Molecular Virology, International Centre for Genetic Engineering and Biotechnology, Padriciano 99, 34149 Trieste, Italy.
Biophysics Institute, CNR-IBF, Via Celoria 26, 20133 Milano, Italy.
Viruses. 2022 May 27;14(6):1157. doi: 10.3390/v14061157.
Pyridobenzothiazolone derivatives are a promising class of broad-spectrum antivirals. However, the mode of action of these compounds remains poorly understood. The HeE1-17Y derivative has already been shown to be a potent compound against a variety of flaviviruses of global relevance. In this work, the mode of action of HeE1-17Y has been studied for West Nile virus taking advantage of reporter replication particles (RRPs). Viral infectivity was drastically reduced by incubating the compound with the virus before infection, thus suggesting a direct interaction with the viral particles. Indeed, RRPs incubated with the inhibitor appeared to be severely compromised in electron microscopy analysis. HeE1-17Y is active against other enveloped viruses, including SARS-CoV-2, but not against two non-enveloped viruses, suggesting a virucidal mechanism that involves the alteration of the viral membrane.
吡啶并苯并噻唑酮衍生物是一类有前途的广谱抗病毒药物。然而，这些化合物的作用模式仍知之甚少。HeE1-17Y 衍生物已被证明是一种针对多种具有全球相关性的黄病毒的有效化合物。在这项工作中，利用报告复制颗粒 (RRPs) 研究了 HeE1-17Y 对西尼罗河病毒的作用模式。在感染前用化合物孵育病毒会大大降低病毒的感染力，因此表明它与病毒颗粒直接相互作用。事实上，用抑制剂孵育的 RRPs 在电子显微镜分析中似乎受到严重损害。HeE1-17Y 对包括 SARS-CoV-2 在内的其他包膜病毒有效，但对两种非包膜病毒无效，这表明其具有病毒杀伤机制，涉及病毒膜的改变。
