Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, Russia.
N.F. Gamaleya National Research Center for Epidemiology and Microbiology, Ivanovsky Institute of Virology, Ministry of Health of the Russian Federation, 123098 Moscow, Russia.
Int J Mol Sci. 2022 Jan 30;23(3):1610. doi: 10.3390/ijms23031610.
Since the beginning of the HIV epidemic, lasting more than 30 years, the main goal of scientists was to develop effective methods for the prevention and treatment of HIV infection. Modern medicines have reduced the death rate from AIDS by 80%. However, they still have side effects and are very expensive, dictating the need to search for new drugs. Earlier, it was shown that phospholipases A2 (PLA2s) from bee and snake venoms block HIV replication, the effect being independent on catalytic PLA2 activity. However, the antiviral activity of human PLA2s against Lentiviruses depended on catalytic function and was mediated through the destruction of the viral membrane. To clarify the role of phospholipolytic activity in antiviral effects, we analyzed the anti-HIV activity of several snake PLA2s and found that the mechanisms of their antiviral activity were similar to that of mammalian PLA2. Our results indicate that snake PLA2s are capable of inhibiting syncytium formation between chronically HIV-infected cells and healthy CD4-positive cells and block HIV binding to cells. However, only dimeric PLA2s had pronounced virucidal and anti-HIV activity, which depended on their catalytic activity. The ability of snake PLA2s to inactivate the virus may provide an additional barrier to HIV infection. Thus, snake PLA2s might be considered as candidates for lead molecules in anti-HIV drug development.
自艾滋病流行 30 多年以来，科学家们的主要目标一直是开发预防和治疗 HIV 感染的有效方法。现代药物已将艾滋病死亡率降低了 80%。然而，它们仍然存在副作用且非常昂贵，这促使人们需要寻找新的药物。早期研究表明，来自蜂和蛇毒液的磷脂酶 A2 (PLA2s) 可阻断 HIV 的复制，其效果与催化 PLA2 活性无关。然而，人类 PLA2s 对慢病毒的抗病毒活性取决于催化功能，并通过破坏病毒膜来介导。为了阐明磷脂酶解活性在抗病毒作用中的作用，我们分析了几种蛇 PLA2 的抗 HIV 活性，发现它们的抗病毒机制与哺乳动物 PLA2 相似。我们的结果表明，蛇 PLA2 能够抑制慢性 HIV 感染细胞与健康 CD4 阳性细胞之间的合胞体形成，并阻止 HIV 与细胞的结合。然而，只有二聚 PLA2 具有明显的杀病毒和抗 HIV 活性，这取决于它们的催化活性。蛇 PLA2 使病毒失活的能力可能为 HIV 感染提供了额外的屏障。因此，蛇 PLA2 可能被视为抗 HIV 药物开发的先导分子候选物。
