Meek T D, Lambert D M, Dreyer G B, Carr T J, Tomaszek T A, Moore M L, Strickler J E, Debouck C, Hyland L J, Matthews T J
Department of Medicinal Chemistry, Smith Kline & French Laboratories, King of Prussia, Pennsylvania 19406.
Nature. 1990 Jan 4;343(6253):90-2. doi: 10.1038/343090a0.
The gag and pol genes of the human immunodeficiency virus type 1 (HIV-1) (ref. 1) are translated as two polyproteins, Pr55gag and Pr160gag-pol (refs 2-6), which are subsequently cleaved by the action of a virus-encoded protease into the four structural gag proteins of the virion core (p17, p24, p7 and p6) and the pol-encoded enzymes essential for retrovirus replication (protease, reverse transcriptase, ribonuclease H, and endonuclease). Mutational inactivation of the proteases of HIV-1 and other retroviruses results in immature, non-infectious virions, indicating that exogenous inhibition of the protease may represent an attractive approach to anti-AIDS therapy. Here we demonstrate that synthetic peptide analogues, which are potent inhibitors of purified HIV-1 protease, inhibit the processing of the viral polyproteins in cultures of HIV-1-infected T lymphocytes and attenuate viral infectivity.
人类免疫缺陷病毒1型（HIV-1）的gag和pol基因（参考文献1）被翻译为两种多聚蛋白，即Pr55gag和Pr160gag-pol（参考文献2 - 6），随后它们在病毒编码蛋白酶的作用下被切割成病毒核心的四种结构gag蛋白（p17、p24、p7和p6）以及逆转录病毒复制所必需的pol编码酶（蛋白酶、逆转录酶、核糖核酸酶H和内切核酸酶）。HIV-1和其他逆转录病毒蛋白酶的突变失活会导致产生未成熟的、无感染性的病毒颗粒，这表明对外源蛋白酶的抑制可能是一种有吸引力的抗艾滋病治疗方法。在此我们证明，作为纯化HIV-1蛋白酶的有效抑制剂的合成肽类似物，可抑制HIV-1感染的T淋巴细胞培养物中病毒多聚蛋白的加工，并减弱病毒的感染性。
