CAMS Key Laboratory of Antiviral Drug Research, Institute of Medicinal Biotechnology, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.
Beijing Key Laboratory of Antimicrobial Agents, Institute of Medicinal Biotechnology, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.
Front Cell Infect Microbiol. 2019 Aug 7;9:277. doi: 10.3389/fcimb.2019.00277. eCollection 2019.
Hand, foot, and mouth disease (HFMD) is a global health concern, especially in the Asia-Pacific region. HFMD caused by Enterovirus 71 (EV71) and Coxsackievirus A16 (CVA16) infection is usually self-limited but occasionally leads to severe pulmonary edema, neurological complications, and even death. Unfortunately, no effective drugs are currently available in clinical practice for the prevention and treatment of HFMD. Thus, anti-HFMD drugs must be urgently developed. A previous study had reported that lycorine could inhibit EV71 replication. In the present study, we found that LY-55, a lycorine derivative, inhibited the replication of EV71 and CVA16 and provided partial protection to mice from EV71 infection, as indicated by the decreased viral load and protein expression levels in muscles, clinical scores, and increased survival rates of infected mice. Mechanistically, LY-55 was not directly viricidal. Instead, the LY-55-mediated inhibition of EV71 and CVA16 was found to be mechanistically possible, at least in part, through downregulating autophagy, which plays an important role for EV71 and CVA16 replication. These findings suggest that LY-55 could be a potential lead or supplement for the development of anti-HFMD agents in the future.
手足口病（HFMD）是一个全球性的健康问题，特别是在亚太地区。由肠道病毒 71 型（EV71）和柯萨奇病毒 A16 型（CVA16）感染引起的 HFMD 通常是自限性的，但偶尔会导致严重肺水肿、神经系统并发症，甚至死亡。不幸的是，目前临床上没有有效的药物可用于预防和治疗 HFMD。因此，必须紧急开发抗 HFMD 药物。先前的一项研究表明，石蒜碱可抑制 EV71 的复制。在本研究中，我们发现石蒜碱衍生物 LY-55 可抑制 EV71 和 CVA16 的复制，并为感染 EV71 的小鼠提供部分保护，这表现在肌肉中的病毒载量和蛋白表达水平降低、临床评分降低以及感染小鼠的存活率提高。从机制上讲，LY-55 并非直接杀病毒。相反，发现 LY-55 介导的 EV71 和 CVA16 抑制作用至少部分是通过下调自噬来实现的，自噬在 EV71 和 CVA16 的复制中起着重要作用。这些发现表明，LY-55 将来可能成为开发抗 HFMD 药物的潜在先导物或补充物。
