Virus entry

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Daelemans, D., Schols, D., Witvrouw, M., Rannecouque, C., Hatse, S., Door-EN, S.V., Hamy, F., Klimkait, X, Clercq, E.D., and Vandamme, A.-M. A second target for the peptoid Xat/transactivation response element inhibitor CGP64222 Inhibition of human immunodeficiency virus replication by blocking CXC-chemo-kine receptor 4-mediated virus entry. 

Collman RG, Yi Y (1999) Cofactors for human immunodeficiency virus entry into primary macrophages. J Infect Dis 179(Suppl 3) S422-S426... 

Finally, during budding, HIV-1 may also incorporate into its membrane envelope a variety of different molecules, including proteins that may subsequently interact with their counterparts on the host cell membrane (reviewed in ref. 192), resulting in intracellular signaling and facilitation of virus fusion (193,194). However, the incorporation of cell membrane-derived molecules does not appear to be an absolute requirement for virus entry (195), indicating the leading role of CD4 and the coreceptor for any such mechanism. However, this phenomenon may account for lower levels of inhibition when the effects of mutant CD4 and/or chemokine receptor are studied. 

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Another potential class of antivirals is those that interfere with the ability of virus to enter cells. If the virus entry process is inhibited, then spread of infection within an individual might be inhibited. As discussed earlier, HIV virus particles initially attach to cells by way of the cellular receptor for CD4 protein, which is embedded in the surface of normal T lymphocytes and macrophages. Recently, recombinant DNA techniques have been used to make large amounts of a part of the pure CD4 protein. Test-tube experiments have shown that if this CD4 protein fragment is incubated with T lymphocytes or macrophages, it can saturate all the CD4 receptors and prevent subsequent infection with HIV. It is possible that this approach might be effective in people, as well. 

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Zhang HJ, Rothwangl K, Mesecar AD, Sabahi A, Rong LJ, Fong HHS. Lamiridosins, Hepatitis C Virus Entry Inhibitors from Lamium album. Journal of Natural Products 2009 72 2158-2162. 

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Kielian, M. and Jungerwirth, S. (1990) Mechanisms of enveloped virus entry into cells. Mol. Biol. Med., 7, 17-31. 

A number of products exist that are targeted at any of the successive events implicated in the replicative cycle of HIV virus entry, viral adsorption, virus-cell fusion, reverse (RNA —> DNA) transcription, proviral DNA integration, viral (DNA —> RNA) transcription (transactivation), viral (mRNA —> protein) translation, virus release, viral assembly, budding, and maturation... 

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