Abstract：
The enterovirus is a genus of single-stranded, highly diverse positive-sense RNA viruses, including Human Enterovirus A-D and Human Rhinovirus A-C species. They are responsible for numerous diseases and some infections can progress to life-threatening complications, particularly in children or immunocompromised patients. To date, there is no treatment against enteroviruses on the market, except for polioviruses (vaccine) and EV-A71 (vaccine in China). Following a decrease in enterovirus infections during and shortly after the (SARS-Cov2) lockdown, enterovirus outbreaks were once again detected, notably in young children. This reemergence highlights on the need to develop broad-spectrum treatment against enteroviruses. Over the last year, our research team has identified a new class of small-molecule inhibitors showing anti-EV activity. Targeting the well-known hydrophobic pocket in the viral capsid, these compounds show micromolar activity against EV-A71 and a high selectivity index (SI) (5h: EC50, MRC-5 = 0.57 μM, CC50, MRC-5 >20 μM, SI > 35; EC50, RD = 4.38 μM, CC50, RD > 40 μM, SI > 9; 6c: EC50, MRC-5 = 0.29 μM, CC50, MRC-5 >20 μM, SI > 69; EC50, RD = 1.66 μM, CC50, RD > 40 μM, SI > 24; Reference: Vapendavir EC50, MRC-5 = 0.36 μM, CC50, MRC-5 > 20 μM, EC50, RD = 0.53 μM, CC50, RD > 40 μM, SI > 63). The binding mode of these compounds in complex with enterovirus capsids was analyzed and showed a series of conserved interactions. Consequently, 6c and its derivatives are promising candidates for the treatment of enterovirus infections.
摘要：
肠道病毒是一种单链,高度多样化的正义RNA病毒，包括人类肠道病毒A-D和人类鼻病毒A-C。他们负责许多疾病和一些感染可以发展到危及生命的并发症，特别是儿童或免疫功能低下的患者。迄今为止,市场上没有针对肠道病毒的治疗方法，脊髓灰质炎病毒(疫苗)和EV-A71(中国疫苗)除外。在（SARS-Cov2）封锁期间和之后不久，肠道病毒感染有所减少，再次发现肠道病毒爆发，尤其是在年幼的孩子。这种重新出现凸显了开发针对肠道病毒的广谱治疗的必要性。在过去的一年里，我们的研究小组发现了一类新的显示抗EV活性的小分子抑制剂.靶向病毒衣壳中众所周知的疏水口袋，这些化合物显示出对EV-A71的微摩尔活性和高选择性指数（SI）（5h：EC50，MRC-5=0.57μM，CC50,MRC-5>20μM,SI>35;EC50,RD=4.38μM,CC50,RD>40μM,SI>9；6c：EC50，MRC-5=0.29μM，CC50,MRC-5>20μM,SI>69；EC50，RD=1.66μM，CC50,RD>40μM,SI>24;参考:VapendavirEC50,MRC-5=0.36μM,CC50,MRC-5>20μM,EC50,RD=0.53μM,CC50,RD>40μM,SI>63)。分析了这些化合物与肠道病毒衣壳的复合物的结合模式，并显示出一系列保守的相互作用。因此,6c及其衍生物是用于治疗肠道病毒感染的有希望的候选物。
