Instituto de Investigación Biomédica de la UCLM (IB-UCLM), C/Almansa 14, 02008 Albacete, Spain.
Instituto de Investigación Biomédica de la UCLM (IB-UCLM), C/Almansa 14, 02008 Albacete, Spain; Facultad de farmacia, Universidad de Castilla-La Mancha, Av. Dr. José María Sánchez Ibáñez, s/n, 02008 Albacete, Spain.
Virus Res. 2024 Oct;348:199447. doi: 10.1016/j.virusres.2024.199447. Epub 2024 Aug 9.
One third of all emerging infectious diseases are vector-borne, with no licensed antiviral therapies available against any vector-borne viruses. Zika virus and Usutu virus are two emerging flaviviruses transmitted primarily by mosquitoes. These viruses modulate different host pathways, including the PI3K/AKT/mTOR pathway. Here, we report the effect on ZIKV and USUV replication of two AKT inhibitors, Miransertib (ARQ-092, allosteric inhibitor) and Capivasertib (AZD5363, competitive inhibitor) in different mammalian and mosquito cell lines. Miransertib showed a stronger inhibitory effect against ZIKV and USUV than Capivasertib in mammalian cells, while Capivasertib showed a stronger effect in mosquito cells. These findings indicate that AKT plays a conserved role in flavivirus infection, in both the vertebrate host and invertebrate vector. Nevertheless, the specific function of AKT may vary depending on the host species. These findings indicate that AKT may be playing a conserved role in flavivirus infection in both, the vertebrate host and the invertebrate vector. However, the specific function of AKT may vary depending on the host species. A better understanding of virus-host interactions is therefore required to develop new treatments to prevent human disease and new approaches to control transmission by insect vectors.
三分之一的新发传染病是由媒介传播的，而针对任何媒介传播病毒都没有获得许可的抗病毒疗法。寨卡病毒和乌苏图病毒是两种主要通过蚊子传播的新发黄病毒。这些病毒调节不同的宿主途径，包括 PI3K/AKT/mTOR 途径。在这里，我们报告了两种 AKT 抑制剂 Miransertib（变构抑制剂）和 Capivasertib（竞争抑制剂）在不同的哺乳动物和蚊子细胞系中对 ZIKV 和 USUV 复制的影响。Miransertib 在哺乳动物细胞中对 ZIKV 和 USUV 的抑制作用强于 Capivasertib，而 Capivasertib 在蚊子细胞中表现出更强的作用。这些发现表明 AKT 在脊椎动物宿主和无脊椎动物媒介的黄病毒感染中起着保守作用。然而，AKT 的具体功能可能因宿主物种而异。这些发现表明 AKT 可能在脊椎动物宿主和无脊椎动物媒介的黄病毒感染中起着保守作用。然而，AKT 的具体功能可能因宿主物种而异。因此，需要更好地了解病毒-宿主相互作用，以开发新的治疗方法来预防人类疾病，并采取新的方法来控制昆虫媒介的传播。
