Mechanism of spontaneous degradation observed in the insertioncontaining HIV-1 Capsid proteins

我们之前报道过，Gag 衣壳蛋白 (CA) 某些位置的氨基酸 (AA) 插入导致 CA 显着降解，并且这种含有 AA 插入的 HIV-1 变体显着损害了感染性和复制能力。我们尝试根据之前的数据鉴定能够与 CA 结合的小化合物。我们使用虚拟对接模拟计算了超过 800 万种化合物与 CA 上假定目标空腔的结合分数，并使用基于细胞的测定评估了它们的抗 HIV-1 活性。通过这些方法我们发现了29种可以抑制HIV-1复制的化合物。

We previously reported that amino acid (AA) insertions at certainpositions of Gag Capsid proteins (CA) caused significant CA degradation, and such AAinsert-containing HIV-1 variants had significantly compromised infectivity andreplication capacity. We attempted to identify small compounds capable of binding to CAbased on our previous data. We calculated binding scores of more than 8 million compoundswith the putative target cavity on CA using virtual docking simulation and evaluatingtheir anti-HIV-1 activity using the cell-based assay. We could find 29 compounds whichcan inhibit replication of HIV-1 by these methods.