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HIV Life Cycle

In order for HIV replication to occur viral membranes must first fuse with target cell membranes and HIV matrix and capsid proteins eventually disassemble. Fusion and uncoating as potential targets are being pursued through structural studies of the p24 capsid protein,1 the p17 matrix protein, and the fusigenic regions of gp41.

A similar approach successfully identified inhibitors of picornavirus replication2. T22, a synthetic peptide of 18 amino acids that is an analog polyphemusin II (an antimicrobial peptide found in the hemocytes of American horseshoe crabs, Limulus polyphemus), appears to be a very potent inhibitor of HIV viral fusion or uncoating3.

T22 has more recently been shown to inhibit the interaction between CXCR-4 and the HIV envelope protein4.

The aromatic polycyclic dione compounds, hypericin and pseudohypericin, have also been reported to confer high stability on the HIV capsid structure that may inhibit HIV uncoating. Hypericin was the first anthraquinone found to inhibit HIV replication in cell culture and inretroviral infections in animals5, 6, 7.


  1. Rossmann M.G. Antiviral agents targeted to interact with viral capsid proteins and a possible application to human immunodeficiency virus. PROC NATL ACAD SCI USA 85:4625-4627 (1988).
  2. Diana, G.D.; Pevear, D.C.; OTTO, M.J.; ET AL. Inhibitors of viral uncoating. PHARMACOL THER 42:289 (1989).
  3. Nakashima, H.; Masuda, M.; Murakami, T.; Koyanagi, Y.; Matsumoto, A.; Fujii, N.; Yamamoto, N., Anti-HIV activity of a novel synthetic peptide, t22 ([tyr-5,12, lys-7]polyphemusin ii): A possible inhibitor of virus-cell fusion ANTIMICROB AGENTS CHEMOTHER 36(6):1249-1255 (1992).
  4. Murakami, T.; Nakajima, T.; Koyanagi, Y.; Tachibana, K.; Fujii, N.; et al. A small molecule cxcr4 inhibitor that blocks T cell line-tropic HIV-1 infection J EXP MED 186(8):1389-1393 (1997).
  5. Lavie, G.; Valentine, F.; Mazur, B.; et al. Studies of the mechanisms of action of the antiretroviral agents hypericin and pseudohypericin. PROC NATL ACAD SCI USA 86:5963-5967 (1989).
  6. Schinazi, R.; Chu, C.K.; Babu, J.R.; Oswald, B.J.; Sallaman, V.; Cannon, D.L.; Eriksson, B. and Nase, M. Anthraquinones as a new class of antiviral agents against human immunodeficiency virus. ANTIVIRAL RES 13:265-2672 (1990).
  7. Lavie, G.; Mazur, Y.; Lavie, D.; Levin, B.; Ittah, Y.; Meruelo, D. Hypericin as an antiretroviral agent: mode of action and related analogues. PROC NATL ACAD SCI USA, 616:556 (1990).


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