Zhang Kexin, Liang Jingyao, Zhang Bingzhi, Huang Lishan, Yu Jianchen, Xiao Xuhan, He Zhenjian, Tao Huaming, Yuan Jie
School of Public Health, Sun Yat-sen University, Guangzhou 510080, China.
Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education, Guangzhou 510080, China.
Molecules. 2024 Feb 23;29(5):978. doi: 10.3390/molecules29050978.
The Zika virus (ZIKV) is a mosquito-borne virus that already poses a danger to worldwide human health. Patients infected with ZIKV generally have mild symptoms like a low-grade fever and joint pain. However, severe symptoms can also occur, such as Guillain-Barré syndrome, neuropathy, and myelitis. Pregnant women infected with ZIKV may also cause microcephaly in newborns. To date, we still lack conventional antiviral drugs to treat ZIKV infections. Marine natural products have novel structures and diverse biological activities. They have been discovered to have antibacterial, antiviral, anticancer, and other therapeutic effects. Therefore, marine products are important resources for compounds for innovative medicines. In this study, we identified a marine natural product, harzianopyridone (HAR), that could inhibit ZIKV replication with EC values from 0.46 to 2.63 µM while not showing obvious cytotoxicity in multiple cellular models (CC > 45 µM). Further, it also reduced the expression of viral proteins and protected cells from viral infection. More importantly, we found that HAR directly bound to the ZIKV RNA-dependent RNA polymerase (RdRp) and suppressed its polymerase activity. Collectively, our findings provide HAR as an option for the development of anti-ZIKV drugs.
寨卡病毒（ZIKV）是一种通过蚊子传播的病毒，已对全球人类健康构成威胁。感染ZIKV的患者通常会出现低烧和关节疼痛等轻微症状。然而，也可能出现严重症状，如吉兰-巴雷综合征、神经病变和脊髓炎。感染ZIKV的孕妇还可能导致新生儿小头畸形。迄今为止，我们仍然缺乏治疗ZIKV感染的传统抗病毒药物。海洋天然产物具有新颖的结构和多样的生物活性。已发现它们具有抗菌、抗病毒、抗癌和其他治疗作用。因此，海洋产物是创新药物化合物的重要资源。在本研究中，我们鉴定出一种海洋天然产物，哈茨吡咯酮（HAR），其在多个细胞模型中能够抑制ZIKV复制，半数有效浓度（EC）值为0.46至2.63 μM，同时未表现出明显的细胞毒性（细胞毒性浓度>45 μM）。此外，它还降低了病毒蛋白的表达，并保护细胞免受病毒感染。更重要的是，我们发现HAR直接与ZIKV的RNA依赖性RNA聚合酶（RdRp）结合，并抑制其聚合酶活性。总的来说，我们的研究结果为抗ZIKV药物的开发提供了HAR这一选择。
