Elshahawi Hesham, Syed Hassan Sharifah, Balasubramaniam Vinod
Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Jalan Lagoon Selatan, Subang Jaya 47500, Selangor, Malaysia.
Tropical Medicine & Biology Multidisciplinary Platform, Monash University Malaysia, Jalan Lagoon Selatan, Subang Jaya 47500, Selangor, Malaysia.
Pathogens. 2019 Sep 30;8(4):169. doi: 10.3390/pathogens8040169.
Zika virus is the latest addition to an ever-growing list of arboviruses that are causing outbreaks with serious consequences. A few mild cases were recorded between 1960 and 1980 until the first major outbreak in 2007 on Yap Island. This was followed by more severe outbreaks in French Polynesia (2013) and Brazil (2015), which significantly increased both syndrome and microcephaly cases. No current vaccines or treatments are available, however, recent studies have taken interest in the NS5 protein which encodes both the viral methyltransferase and RNA-dependent RNA polymerase. This makes it important for viral replication alongside other important functions such as inhibiting the innate immune system thus ensuring virus survival and replication. Structural studies can help design inhibitors, while biochemical studies can help understand the various mechanisms utilized by NS5 thus counteracting them might inhibit or abolish the viral infection. Drug repurposing targeting the NS5 protein has also proven to be an effective tool since hundreds of thousands of compounds can be screened therefore saving time and resources, moreover information on these compounds might already be available especially if they are used to treat other ailments.
寨卡病毒是不断增加的虫媒病毒名单中的最新成员,这些病毒正在引发具有严重后果的疫情。1960年至1980年间记录了几例轻症病例,直到2007年在雅浦岛首次发生重大疫情。随后在法属波利尼西亚(2013年)和巴西(2015年)爆发了更严重的疫情,这显著增加了综合征和小头畸形病例。目前尚无可用的疫苗或治疗方法,然而,最近的研究对编码病毒甲基转移酶和RNA依赖性RNA聚合酶的NS5蛋白产生了兴趣。这使得它对于病毒复制以及其他重要功能(如抑制先天免疫系统从而确保病毒存活和复制)都很重要。结构研究有助于设计抑制剂,而生化研究有助于了解NS5利用的各种机制,因此对抗这些机制可能会抑制或消除病毒感染。靶向NS5蛋白的药物重新利用也已被证明是一种有效的工具,因为可以筛选数十万种化合物,从而节省时间和资源,此外,关于这些化合物的信息可能已经存在,特别是如果它们用于治疗其他疾病的话。