Reverse transcriptase precursor processing

The HlV-1 protease is responsible for processing the protein precursors to the enzymes (integrase, protease and reverse transcriptase) and the structural proteins of the HIV-1 virus. Maw and Hall found that topological indices provide rehable QSAR models for the IC50 data of 32 HIV-1 protease inhibitors [29]. The best QSAR model, with r = 0.86, s=0.60 and q = 0.79, was obtained with the shape index Ka, the connechvity index the sum of HE-state indices for ah groups that act as... 

There are several others that inhibit DNA replication. Fagaronine and nitidine have ben mentioned previously as intercalating agents, and this intercalation evidently inhibits the action of DNA polymerase [334]. Several benzophenanthridines and protoberberines inhibit reverse transcriptase, which catalyzes the synthesis of DNA with an RNA template [356, 357]. Mimosine at the cellular level, rather than directly on the process, is an inhibitor of DNA synthesis because it chelates iron [358] and because it blocks the synthesis of thymidylate, an essential precursor of DNA [359]. Vincristine may also act as an inhibitor of thymidylate synthesis, perhaps because it alkylates an essential thiol group of an enzyme [360]. 

Fig. 43.2. Replicative cycle of HIV. (1) The virus gp120 protein binds to CD4 resulting in fusion of the viral envelope and the cellular membrane and the release of viral nucleocapsid into the cytoplasm. (2) The nucleocapsid is uncoated, and viral RNA is reverse transcribed by reverse transcriptase (RT). (3) The resulting double-stranded proviral DMA migrates into the cell nucleus and is integrated into the cellular DMA by integrase (IN). (4) Proviral DNA is transcribed by the cellular RNA polymerase II. (5) The mRNAs are translated by the cellular polysomes. (6) Viral proteins and genomic RNA are transported to the cellular membrane and assemble. Immature virions are released, and polypeptide precursors are processed by the viral protease (PR) to produce mature vital particles. (Adapted from Sierra S, Kupfer B, Kaiser R. Basics of the virology of HIV-1 and its replication. J Clin Virol 2005 34 233 with permission from Elsevier.)...

It is interesting to note that, using complementary DNA (cDNA) (Chapter 14), that is, DNA obtained by synthesis from a messenger RNA (mRNA) template in a reaction catalyzed by reverse transcriptase enzyme, the norcoclaurine synthase enzyme has been characterized, and the pathway from the precursors has been shown to most likely involve imine formation and then cyclization in a process resembling the Pictet-Spengler reaction. ... 

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