近年来,由病毒感染引起的传染病严重危害人类健康,特别是由SARS-CoV-2引起的COVID-19,它继续在全球蔓延。迫切需要开发广谱抗病毒抑制剂。这里,我们报道了一系列被证明对人类冠状病毒(HCoV)有效的小分子化合物,如SARS-CoV-2及其相关变种(VOC),包括Alpha(B.1.1.7),Beta(B.1.351),Gamma(P.1),Delta(B.1.617.2),和Omicron(B.1.1.529),SARS-CoV,MERS-CoV,HCoV-OC43和其他具有I类病毒融合蛋白的病毒,如流感病毒,埃博拉病毒(EBOV)尼帕病毒(NiV),拉沙热病毒(LASV)。它们还有效对抗以ZIKV为代表的II类包膜病毒和以水泡性口炎病毒(VSV)为代表的III类包膜病毒。进一步的研究表明,这些化合物可能通过多种机制发挥抗病毒作用,包括抑制六螺旋束的形成,这是包膜病毒与细胞膜融合的典型特征,和/或靶向病毒膜以灭活无细胞病毒体。这些化合物有望成为抗SARS-CoV-2和其他包膜病毒的候选药物。
In recent years, infectious diseases caused by viral infections have seriously endangered human health, especially COVID-19, caused by SARS-CoV-2, which continues to spread worldwide. The development of broad-spectrum antiviral inhibitors is urgently needed. Here, we report a series of small-molecule compounds that proved effective against human coronaviruses (HCoV), such as SARS-CoV-2 and its variants of concern (VOCs), including Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2), and Omicron (B.1.1.529), SARS-CoV, MERS-CoV, HCoV-OC43, and other viruses with class I viral fusion proteins, such as influenza virus, Ebola virus (EBOV), Nipah virus (NiV), and Lassa fever virus (LASV). They are also effective against class II enveloped viruses represented by ZIKV and class III enveloped viruses represented by vesicular stomatitis virus (VSV). Further studies have shown that these compounds may exert antiviral effects through a variety of mechanisms, including inhibiting the formation of the six-helix bundle, which is a typical feature of enveloped virus fusion with cell membranes, and/or targeting viral membrane to inactivate cell-free virions. These compounds are expected to become drug candidates against SARS-CoV-2 and other enveloped viruses.