Action of Anti-HIV Drugs and Resistance: Reverse Transcriptase Inhibitors and Protease Inhibitors

The HIV replicative cycle reveals several virus-specific events that could function as targets for chemotherapeutic intervention. The compounds that are presently available as anti-HIV drugs are targeted at either the substrate binding site of the reverse transcriptase (zidovudine, didanosine, zalcitabine, stavudine, lamivudine) or a non-substrate binding site of the reverse transcriptase (nevirapine, delavirdine), or the viral protease (saquinavir, ritonavir, indinavir, nelfinavir). Remarkable clinical efficacy has been observed with combinations of different reverse transcriptase inhibitors and protease inhibitors. It may be anticipated that with the advent of newer and more efficient compounds the effectiveness of HIV inhibition could still be improved upon and the prospects for a definitive cure of the disease may be accomplished. An account with 107 references.

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Anti-HIV Drug Discovery, Development and Synthesis of Delavirdine: Review Article

International Research Journal of Pure and Applied Chemistry ◽

10.9734/irjpac/2019/v20i330137 ◽

2019 ◽

pp. 1-16 ◽

Cited By ~ 1

Author(s):

Wollela Behja ◽

Mudin Jemal

Keyword(s):

Life Cycle ◽

Reverse Transcriptase ◽

Genetic Material ◽

Amino Acid Sequences ◽

Surface Binding ◽

Reverse Transcriptase Inhibitors ◽

Fusion Inhibitors ◽

Critical Components ◽

Hiv Drugs ◽

Anti Hiv

Viruses are the smallest infectious agents of animal and plant tissues. Viruses are totally dependent on living cells to survive as they utilize the host cell's own replication processes, in order to reproduce themselves. HIV is the causative agent of AIDS. HIV is an unusually difficult to treat because it incorporate its own genetic material into the genome of an infected host cell. It infects T cells that carry the CD4 antigen on their surface. Binding and fusion, reverse transcription, integration, transcription, assembly and budding are the major steps of the HIV life cycle. The HIV/AIDS disease is treated by interrupting the HIV life cycle with specially designed drugs. The discovery of effective drugs against HIV has focused on targeting various critical components of the replication cycle of HIV. Depending on the target within the HIV replicative cycle they interact with, anti-HIV compounds are categorized into six groups. These are: nucleoside (nucleotide) reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), cell entry inhibitors or fusion inhibitors (FIs), co-receptor inhibitors (CRIs) and integrase inhibitors (INIs). The development of effective anti-HIV drugs is difficult due to wide variations in nucleotide and amino acid sequences. The development of anti-HIV drug passes through several important steps. This includes development from α-APA to ITU, ITU to DATA, DAPY to etravirine. Fosdevirine, lersivirine and rilpivirine are among the drugs that were undergoing clinical development and finally only rilpivirine was approved by FDA. The synthesis of delavirdine employs the use of heterocyclic rings like substituted pyridine and indole.

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Anti-Human Immunodeficiency Virus Interactions of SCH-C (SCH 351125), a CCR5 Antagonist, with Other Antiretroviral Agents In Vitro

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.46.5.1336-1339.2002 ◽

2002 ◽

Vol 46 (5) ◽

pp. 1336-1339 ◽

Cited By ~ 68

Author(s):

Cécile L. Tremblay ◽

Françoise Giguel ◽

Christopher Kollmann ◽

Yongbiao Guan ◽

Ting-Chao Chou ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Reverse Transcriptase ◽

Protease Inhibitors ◽

Reverse Transcriptase Inhibitors ◽

Antiretroviral Agents ◽

Synergistic Interactions ◽

Immunodeficiency Virus ◽

Anti Hiv ◽

Hiv 1

ABSTRACT SCH-C (SCH 351125) is a small-molecule antagonist of the human immunodeficiency virus type 1(HIV-1) coreceptor CCR5. It has in vitro activity against R5 viruses with 50% inhibitory concentrations ranging from 1.0 to 30.9 nM. We have studied anti-HIV-1 interactions of SCH-C with other antiretroviral agents in vitro. Synergistic interactions were seen with nucleoside reverse transcriptase inhibitors (zidovudine and lamivudine), nonnucleoside reverse transcriptase inhibitors (efavirenz), and protease inhibitors (indinavir) at all inhibitory concentrations evaluated. We have also studied antiviral interactions between the HIV-1 fusion inhibitor T-20 and SCH-C against a panel of R5 HIV-1 isolates. We found synergistic interactions against all the viruses tested, some of which harbored resistance mutations to reverse transcriptase and protease inhibitors. Anti-HIV-1 synergy was also observed between SCH-C and another R5 virus inhibitor, aminooxypentane-RANTES. These findings suggest that SCH-C may be a useful anti-HIV drug in combination regimens and that a combination of chemokine coreceptor/fusion inhibitors may be useful in the treatment of multidrug-resistant viruses.

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A Review of Electroanalytical Techniques for Determination of Anti-HIV Drugs

International Journal of Electrochemistry ◽

10.4061/2011/343947 ◽

2011 ◽

Vol 2011 ◽

pp. 1-17 ◽

Cited By ~ 10

Author(s):

Burçin Bozal ◽

Bengi Uslu ◽

Sibel A. Özkan

Keyword(s):

Reverse Transcriptase ◽

Immune Deficiency Syndrome ◽

Deficiency Syndrome ◽

Reverse Transcriptase Inhibitors ◽

Pharmaceutical Dosage Forms ◽

Fusion Inhibitors ◽

Voltammetric Techniques ◽

Hiv Drugs ◽

Anti Hiv

Until now after the human immunodeficiency virus (HIV) was discovered as the then tentative aetiological agent of acquired immune deficiency syndrome (AIDS), exactly 25 anti-HIV compounds have been formally approved for clinical use in the treatment of AIDS. These compounds fall into six categories: nucleoside reverse transcriptase inhibitors (NRTIs: zidovudine, didanosine, zalcitabine, lamivudine, abacavir, stavudine, and emtricitabine), nucleotide reverse transcriptase inhibitors (NtRTIs: tenofovir), nonnucleoside reverse transcriptase inhibitors (NNRTIs: efavirenz, nevirapine, delavirdine, and etravirine), protease inhibitors (PIs: ritonavir, indinavir, saquinavir, nelfinavir, amprenavir, lopinavir, fosamprenavir, atazanavir, tipranavir and darunavir), fusion inhibitors (FIs: enfuvirtide), coreceptor inhibitors (CRIs: maraviroc), and integrase inhibitors (INIs: raltegravir). The present paper submitted the use of various electroanalytical techniques for the determination of anti-HIV drugs. This paper covers the time period from 1990 to 2010 including voltammetric techniques that were reported. Presented application concerns analysis of anti-HIV drugs from pharmaceutical dosage forms and biological samples.

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Synthetic Development of Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) as Anti-HIV Drugs: Efavirenz and its Derivatives

Current Organic Chemistry ◽

10.2174/1385272821666170420180122 ◽

2017 ◽

Vol 21 (21) ◽

Cited By ~ 1

Author(s):

Jian Zhang ◽

Yong Wang

Keyword(s):

Reverse Transcriptase ◽

Reverse Transcriptase Inhibitors ◽

Nucleoside Reverse Transcriptase Inhibitors ◽

Hiv Drugs ◽

Anti Hiv

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Twenty-six years of HIV science: an overview of anti-HIV drugs metabolism

Brazilian Journal of Pharmaceutical Sciences ◽

10.1590/s1984-82502011000200003 ◽

2011 ◽

Vol 47 (2) ◽

pp. 209-230 ◽

Cited By ~ 6

Author(s):

Carolina Horta Andrade ◽

Lenis Medeiros de Freitas ◽

Valéria de Oliveira

Keyword(s):

Reverse Transcriptase ◽

Pharmacokinetic Profile ◽

Antiretroviral Drugs ◽

Reverse Transcriptase Inhibitors ◽

Nucleoside Reverse Transcriptase Inhibitors ◽

Entry Inhibitors ◽

Fusion Inhibitors ◽

Hiv Research ◽

Hiv Drugs ◽

Anti Hiv

From the identification of HIV as the agent causing AIDS, to the development of effective antiretroviral drugs, the scientific achievements in HIV research over the past twenty-six years have been formidable. Currently, there are twenty-five anti-HIV compounds which have been formally approved for clinical use in the treatment of AIDS. These compounds fall into six categories: nucleoside reverse transcriptase inhibitors (NRTIs), nucleotide reverse transcriptase inhibitors (NtRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), cell entry inhibitors or fusion inhibitors (FIs), co-receptor inhibitors (CRIs), and integrase inhibitors (INIs). Metabolism by the host organism is one of the most important determinants of the pharmacokinetic profile of a drug. Formation of active or toxic metabolites will also have an impact on the pharmacological and toxicological outcomes. Therefore, it is widely recognized that metabolism studies of a new chemical entity need to be addressed early in the drug discovery process. This paper describes an overview of the metabolism of currently available anti-HIV drugs.

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