Human immunodeficiency virus cleavage sites

At the present time, there are at least 14 compounds that have been formally approved for the treatment of human immunodeficiency virus (HIV) infections. There are six nucleoside reverse transcriptase inhibitors (NRTIs) that, after their intracellular conversion to the 5 -triphosphate form, are able to interfere as competitive inhibitors of the normal substrates (dNTPs). These are zidovudine (AZT), didanosine (ddl), zalcitabine (ddC), stavudine (d4T), lamivudine (3TC), and abacavir (ABC). There are three nonnucleoside reverse transcriptase inhibitors (NNRTIs) — nevirapine, delavirdine, and efavirenz — that, as such, directly interact with the reverse transcriptase at a nonsubstrate binding, allosteric site. There are five HIV protease inhibitors (Pis saquinavir, ritonavir, indinavir, nelfinavir, and amprenavir) that block the cleavage of precursor to mature HIV proteins, thus impairing the infectivity of the virus particles produced in the presence of these inhibitors. 

Wiegers, K. Rutter, G. Kottler, H. Tessmer, U. Hohenberg, H. Krausslich, H. G. Sequential steps in human immunodeficiency virus particle maturation revealed by alterations of individual Gag polyprotein cleavage sites. J. Virol, 1998, 72 2846-2854. 

M. Prabu-Jeyabalan, E.A. Nalivaika, N.M. King, C.A. Schiffer, Structural basis for coevolution of a human immunodeficiency virus type 1 nucleocapsid-pl cleavage site with a v82a drug-resistant mutation in viral protease,/. Virol. 2004, 78(22), 12446-54. 

Human immunodeficiency virus (HIV) is the etiological agent of acquired immune deficiency syndrome (AIDS). The replication of the HIV requires a viral aspartyl protease (HIV protease) to process the virally encoded gag and gag-pol polyproteins. These cleavage events release enzymes and structural proteins that are essential for the assembly of infectious viral particles. Inhibition of HIV protease activity in infected cells thus leads to the production of an immature, noninfectious virus. HIV protease (PR) differs from monomeric aspartyl proteases in that the active site is formed by the assembly of two 99 amino acid polypeptides into a functional homodimer. 

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