PDF(Pubmed)
Abstract：
Zika virus (ZIKV) is one of the mosquito-borne flaviviruses that exhibits a unique tropism to nervous systems and is associated with Guillain-Barre syndrome and congenital Zika syndrome (CZS). Dengue virus (DENV) and yellow fever virus (YFV), the other two mosquito-borne flaviviruses, have also been circulating for a long time and cause severe diseases, such as dengue hemorrhagic fever and yellow fever, respectively. However, there are no safe and effective antiviral drugs approved for the treatment of infections or coinfections of these flaviviruses. Here, we found that zafirlukast, a pregnancy-safe leukotriene receptor antagonist, exhibited potent antiviral activity against infections of ZIKV strains from different lineages in different cell lines, as well as against infections of DENV-2 and YFV 17D. Mechanistic studies demonstrated that zafirlukast directly and irreversibly inactivated these flaviviruses by disrupting the integrity of the virions, leading to the loss of viral infectivity, hence inhibiting the entry step of virus infection. Considering its efficacy against flaviviruses, its safety for pregnant women, and its neuroprotective effect, zafirlukast is a promising candidate for prophylaxis and treatment of infections or coinfections of ZIKV, DENV, and YFV, even in pregnant women.
摘要：
寨卡病毒（ZIKV）是蚊媒黄病毒之一，对神经系统表现出独特的嗜性，并与格林-巴利综合征和先天性寨卡综合征（CZS）有关。登革热病毒（DENV）和黄热病病毒（YFV），另外两种蚊媒黄病毒，也已经传播了很长时间并导致严重的疾病，如登革热出血热和黄热病，分别。然而,目前还没有安全有效的抗病毒药物被批准用于治疗这些黄病毒的感染或合并感染。这里,我们发现扎鲁司特,一种怀孕安全的白三烯受体拮抗剂，在不同细胞系中对来自不同谱系的ZIKV菌株的感染表现出有效的抗病毒活性，以及针对DENV-2和YFV17D的感染。机制研究表明，扎鲁司特通过破坏病毒体的完整性，直接和不可逆地灭活这些黄病毒，导致病毒感染性的丧失，从而抑制病毒感染的进入步骤。考虑到它对黄病毒的功效，它对孕妇的安全性，以及它的神经保护作用，扎鲁司特是预防和治疗ZIKV感染或合并感染的有前途的候选药物，DENV,YFV,即使是孕妇。
