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Inhibition of HIV-1 protease in infected T-lymphocytes by synthetic peptide analogues

Abstract

THE gag and pol genes of the human immunodeficiency virus type 1 (HIV-1) (ref. 1) are translated as two polyproteins, Pr55gag and Prl60gag-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 (pi7, p24, p7 and p6)7–9and the pol-encoded enzymes essential for retrovirus replication (protease, reverse transcriptase, ribonuclease H, and endonuclease). Mutational inactivation of the proteases of HIV-110–13 and other retro viruses14,15results 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.

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Meek, T., Lambert, D., Dreyer, G. et al. Inhibition of HIV-1 protease in infected T-lymphocytes by synthetic peptide analogues. Nature 343, 90–92 (1990). https://doi.org/10.1038/343090a0

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