Kumar Vathan, Shin Jin Soo, Shie Jiun-Jie, Ku Keun Bon, Kim Chonsaeng, Go Yun Young, Huang Kai-Fa, Kim Meehyein, Liang Po-Huang
Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan.
Korea Research Institute of Chemical Technology, Daejeon, Republic of Korea.
Antiviral Res. 2017 May;141:101-106. doi: 10.1016/j.antiviral.2017.02.007. Epub 2017 Feb 17.
Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe acute respiratory illness with fever, cough and shortness of breath. Up to date, it has resulted in 1826 human infections, including 649 deaths. Analogous to picornavirus 3C protease (3C), 3C-like protease (3CL) is critical for initiation of the MERS-CoV replication cycle and is thus regarded as a validated drug target. As presented here, our peptidomimetic inhibitors of enterovirus 3C (6b, 6c and 6d) inhibited 3CL of MERS-CoV and severe acute respiratory syndrome coronavirus (SARS-CoV) with IC values ranging from 1.7 to 4.7 μM and from 0.2 to 0.7 μM, respectively. In MERS-CoV-infected cells, the inhibitors showed antiviral activity with EC values ranging from 0.6 to 1.4 μM, by downregulating the viral protein production in cells as well as reducing secretion of infectious viral particles into culture supernatants. They also suppressed other α- and β-CoVs from human and feline origin. These compounds exhibited good selectivity index (over 70 against MERS-CoV) and could lead to the development of broad-spectrum antiviral drugs against emerging CoVs and picornaviruses.
中东呼吸综合征冠状病毒（MERS-CoV）可引发伴有发热、咳嗽和呼吸急促的严重急性呼吸道疾病。截至目前，它已导致1826人感染，其中649人死亡。与小RNA病毒3C蛋白酶（3C）类似，3C样蛋白酶（3CL）对于MERS-CoV复制周期的启动至关重要，因此被视为一个经过验证的药物靶点。如本文所述，我们的肠道病毒3C肽模拟抑制剂（6b、6c和6d）对MERS-CoV和严重急性呼吸综合征冠状病毒（SARS-CoV）的3CL均有抑制作用，其IC值分别为1.7至4.7μM和0.2至0.7μM。在感染MERS-CoV的细胞中，这些抑制剂通过下调细胞内病毒蛋白的产生以及减少感染性病毒颗粒向培养上清液中的分泌，表现出抗病毒活性，其EC值为0.6至1.4μM。它们还能抑制其他源自人类和猫科动物的α和β冠状病毒。这些化合物表现出良好的选择性指数（对MERS-CoV超过70），并可能促成针对新兴冠状病毒和小RNA病毒的广谱抗病毒药物的研发。
