Raekiansyah Muhareva, Mori Mihoko, Nonaka Kenichi, Agoh Masanobu, Shiomi Kazuro, Matsumoto Atsuko, Morita Kouichi
Department of Virology, Institute of Tropical Medicine, Nagasaki University, 1-12-4 Sakamoto, Nagasaki, 852-8523 Japan.
Kitasato Institute for Life Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8641 Japan.
Trop Med Health. 2017 Oct 26;45:32. doi: 10.1186/s41182-017-0072-7. eCollection 2017.
Microbial natural products possess a wide range of biological and biochemical potential. Among them, fungal secondary metabolites are one of the most important sources for discovering new drugs or lead compounds. In the present study, we explored substances produced by the strain sp. FKI-7127 for its antiviral activity. We identified brefeldin A as a novel antiviral agent against dengue viruses. The inhibitory effect of brefeldin A was confirmed by virus titer and immunofluorescence assay. Brefeldin A inhibited dengue viruses regardless of serotypes and other related viruses including Zika virus and Japanese encephalitis virus. Time-of-addition study showed that brefeldin A exerts its antiviral effect at an early stage of the dengue virus (DENV) life cycle. These studies demonstrate that (i) brefeldin A could be used as a lead compound for drug development of anti-DENV and other related viruses and (ii) fungal metabolites are a potential and valuable source for dengue virus drug discovery.
微生物天然产物具有广泛的生物学和生物化学潜力。其中，真菌次级代谢产物是发现新药或先导化合物的最重要来源之一。在本研究中，我们探索了菌株sp. FKI-7127产生的物质的抗病毒活性。我们鉴定出布雷菲德菌素A是一种新型抗登革病毒剂。通过病毒滴度和免疫荧光测定证实了布雷菲德菌素A的抑制作用。布雷菲德菌素A对登革病毒具有抑制作用，无论其血清型如何，对包括寨卡病毒和日本脑炎病毒在内的其他相关病毒也有抑制作用。添加时间研究表明，布雷菲德菌素A在登革病毒（DENV）生命周期的早期发挥其抗病毒作用。这些研究表明：（i）布雷菲德菌素A可作为抗DENV和其他相关病毒药物开发的先导化合物；（ii）真菌代谢产物是登革病毒药物发现的潜在且有价值的来源。
