Human immunodeficiency virus enzyme inhibition

Crixivan inhibits an enzyme called HIV (human immunodeficiency virus) protease. 

Thiourea compounds have been observed to inhibit human immunodeficiency virus (HIV) reverse transcriptase, a viral enzyme that is responsible for the reverse transcription of the retroviral RNA to proviral DNA. Phenethylthiazoylthiourea (PETT) compounds were discovered as potent inhibitors of HIV type 1 and display certain structure-activity relationships among various substituents in their structure.199 207 Furthermore, thiourea derivatives have been found to be potent and selective viral inhibitors, antifungal and antibacterial compounds.208 215... 

Up to this point, GIPF expressions have been formulated for only one type of biological activity - the inhibition of reverse transcriptase (RT), the enzyme that promotes the reverse transcription of genomic RNA into double-stranded DNA, a key step in the replication of the human immunodeficiency virus, HIV [82, 87]. Analytical representations were obtained for the anti-HIV potencies of three families of RT inhibitors the correlation coefficients are between 0.930 and 0.952. We are currently investigating the effects of applying the GIPF approach to certain portions of the molecules rather than their entireties. This might reveal the source of the activity, or alternatively, indicate it to be delocalized. 

The rapid spread of acquired immune deficiency syndrome (AIDS) has prompted numerous efforts to develop therapeutic agents against the human immunodeficiency virus type 1 (HIV-1) [2351. Efforts have focused on inhibition of the virally encoded reverse transcriptase (RT) enzyme, which is responsible for the conversion of retroviral RNA to proviral DNA. The nucleoside RT inhibitors 3 -azidothymidine (AZT) and dideoxyinosine (ddl) have proven to be clinically useful anti HIV-1 agents [236], but due to their lack of selectivity versus other DNA polymerases, these compounds are flawed by their inherent toxi-... 

In studies of molecular simplification of catechins targeting both human immunodeficiency virus reverse transcriptase (HIV-RT) and mutated EHV-RT enzymes, we are able to differentiate the polymerase and strand-transfer inhibiting activities... 

Human immunodeficiency virus-1 (HIV-1) protease is an enzyme that breaks inactive polyproteins into their functional parts that are vital for the proper operation of HIV-1. This enzyme is a target for treatment of patients infected with HIV-1. HIV-1 protease operates as a dimeric complex, a trait that lends the enzyme to be inhibited by a drug that is highly symmetrical.24... 

When AIDS (Acquired Immune Deficiency Syndrome) first came into the news in the 1980s it was a horror story of mysterious deaths from normally harmless diseases after the patient s immune system had been weakened and eventually destroyed. The cause was identified by biologists as a new virus HIV (Human Immunodeficiency Virus) and antiviral drugs, notably AZT (Chapter 49), were used with some success. These drugs imitate natural nucleosides (AZT imitates deoxythymidine) and inhibit the virus from copying its RNA into DNA inside human cells by inhibiting the enzyme reverse transcriptase . 

Berberine chloride exhibited reverse transcriptase inhibitory properties against both H1V-1RT (p66/p51)(Human immunodeficiency virus type 1 reverse transcriptaseXIC50 60.9 pg/ml [163.8 (J.M]) and HIV-2RT (p68/p55)(Human immunodeficiency virus type 2 reverse transcriptase)(IC o 57.8 pg/ml [155.5 pM]). The alkaloid is thought to inhibit various RNA and DNA polymerizing enzymes via interaction with nucleic acid template-primers [212]. 

Indinavir sulfate is a protease inhibitor that inhibits human immunodeficiency virus (HIV) protease, the enzyme that cleaves viral polyprotein precursors into functional proteins in HIV-infected cells. Inhibition of this enzyme by indinavir results in formation of immature noninfectious viral particles. It is indicated in the treatment of HIV infection in combination with other antiretroviral agents. 

Ritonavir is an inhibitor of the human immunodeficiency virus (HIV) protease which, in combination with nucleoside analogs (600 mg/b.i.d. p.o.), is indicated in the treatment of HIV infection. Ritonavir is a peptidomimetic inhibitor of both the HIV-1 and HIV-2 proteases. Inhibition of HIV protease renders the enzyme incapable of processing the gag-pol polyprotein precursor, which leads to production of noninfectious immature HIV particles. 

One of the newest and potentially most interesting areas for chemotherapy is the inhibition of proteases. This is of intense pharmaceutical interest for the management of high blood pressure and of viral diseases. The difficulty with this approach lies in the fact that the proteases use common mechanisms in the mammalian host and microorganisms. Nevertheless, specificity of inhibition has been achieved for the mammalian enzyme renin for the control of high blood pressure and for the protease used for replication of the human immunodeficiency virus which causes AIDS. For this reason, there is reason to be encouraged that inhibition of proteases in parasitic organisms will be an effective means of chemotherapy. 

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