Approval of Zidovudine (AZT) for Acquired Immunodeficiency Syndrome

Brook, Itzhak

doi:10.1001/jama.1987.03400110099035

Cited by 33 publications

(11 citation statements)

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“…For example, the first anti-HIV drug zidovudine or azidothymidine (a nucleoside analog) was approved by the Food and Drug Administration (FDA) in 1987. It inhibits HIV reverse transcriptase, hence thwarting viral replication [ 8 ]. PR slices the newly synthesized polyproteins at the relevant positions to form the mature protein apparatus and is a major drug-target for treatment of HIV [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

HIVprotI: an integrated web based platform for prediction and design of HIV proteins inhibitors

et al. 2018

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A number of anti-retroviral drugs are being used for treating Human Immunodeficiency Virus (HIV) infection. Due to emergence of drug resistant strains, there is a constant quest to discover more effective anti-HIV compounds. In this endeavor, computational tools have proven useful in accelerating drug discovery. Although methods were published to design a class of compounds against a specific HIV protein, but an integrated web server for the same is lacking. Therefore, we have developed support vector machine based regression models using experimentally validated data from ChEMBL repository. Quantitative structure activity relationship based features were selected for predicting inhibition activity of a compound against HIV proteins namely protease (PR), reverse transcriptase (RT) and integrase (IN). The models presented a maximum Pearson correlation coefficient of 0.78, 0.76, 0.74 and 0.76, 0.68, 0.72 during tenfold cross-validation on IC50 and percent inhibition datasets of PR, RT, IN respectively. These models performed equally well on the independent datasets. Chemical space mapping, applicability domain analyses and other statistical tests further support robustness of the predictive models. Currently, we have identified a number of chemical descriptors that are imperative in predicting the compound inhibition potential. HIVprotI platform (http://bioinfo.imtech.res.in/manojk/hivproti) would be useful in virtual screening of inhibitors as well as designing of new molecules against the important HIV proteins for therapeutics development.Electronic supplementary materialThe online version of this article (10.1186/s13321-018-0266-y) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 99%

HIVprotI: an integrated web based platform for prediction and design of HIV proteins inhibitors

et al. 2018

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“…Already in 1974, AZT was reported by Ostertag et al [ 36 ] to specifically target the Friend virus strain of murine leukemia virus—a virus closely related to PERV. AZT was also the first drug shown to be effective against HIV-1 [ 37 ], and it was approved by the FDA for the treatment of HIV infection in 1987 [ 38 ].…”

Section: Inhibitors Of Reverse Transcriptasementioning

confidence: 99%

Can Antiretroviral Drugs Be Used to Treat Porcine Endogenous Retrovirus (PERV) Infection after Xenotransplantation?

Denner

2017

Viruses

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Porcine endogenous retroviruses (PERVs) are integrated in the genome of all pigs; they are released as infectious particles, and under certain conditions they can infect human cells. Therefore, they represent a risk when pigs are used as sources of cells, tissues, or organs for xenotransplantation. Xenotransplantation is under development due to the increasing shortage of human transplants. Whereas most porcine microorganisms which may be able to induce a disease (zoonosis) in the transplant recipient can be eliminated, this is not possible in the case of PERVs. Antiretroviral drugs which had been developed for the treatment of human immunodeficiency virus-1 (HIV-1) infections have been tested in vitro for their efficacy in inhibiting PERV replication. Inhibitors of the viral reverse transcriptase and of the integrase have been found effective. The most effective inhibitor of the reverse transcriptase was azidothymidine (AZT); the integrase inhibitors were the most potent inhibitors of PERV. Although in the past PERV transmission has not been observed after experimental or clinical xenotransplantation of pig cells or organs, and although PERVs may one day be inactivated in pigs by genome editing using CRISPR/Cas, knowing which antiretroviral drugs can effectively restrict PERV infection will still be important.

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“…Recently, Xie and colleagues have identified two classes of novel HIV-1 NNRTIs, diarylanilines (DAANs) and diarylpyridines (DAPAs) (see Figure 1 ), with extremely high anti-HIV efficacy and improved resistance profile [ 5 , 6 , 7 , 8 ]. As a further study, we combined new DAPA or DAAN-NNRTIs (i.e., DAPA-2e, DAAN-14h, and DAAN-15h) with azidothymidine (AZT) [ 9 , 10 ] to explore their potential synergistic antiviral effects against laboratory-adapted and primary as well as RTI-resistant HIV-1 strains. Meanwhile, NNRTI drugs nevirapine (NVP) [ 11 ] and etravirine (ETR or TMC125) [ 12 ] were used as controls because the synergy between AZT and NVP [ 13 ] or between AZT and ETR [ 14 ] have been previously reported.…”

Section: Introductionmentioning

confidence: 99%

Combining New Non-Nucleoside Reverse Transcriptase Inhibitors (RTIs) with AZT Results in Strong Synergism against Multi-RTI-Resistant HIV-1 Strains

Wang

et al. 2018

Molecules

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Reverse transcriptase inhibitors (RTIs), including nucleoside RTIs (NRTIs) and non-nucleoside RTIs (NNRTIs), are critical antiretroviral drugs for the treatment of human immunodeficiency virus (HIV) infection. Emergence of multi-RTI resistance calls for the development of more potent therapeutics or regimens against RTI-resistant strains. Here, we demonstrated that combining azidothymidine (AZT) with a new NNRTIs under development, diarylpyridine (DAPA)-2e, diarylanilin (DAAN)-14h, or DAAN-15h, resulted in strong synergism against infection by divergent HIV-1 strains, including those resistant to NRTIs and NNRTIs, suggesting the potential for developing these novel NNRTIs as salvage therapy for HIV/acquired immune deficiency syndrome (AIDS) patients.

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Approval of Zidovudine (AZT) for Acquired Immunodeficiency Syndrome

Cited by 33 publications

References 0 publications

HIVprotI: an integrated web based platform for prediction and design of HIV proteins inhibitors

HIVprotI: an integrated web based platform for prediction and design of HIV proteins inhibitors

Can Antiretroviral Drugs Be Used to Treat Porcine Endogenous Retrovirus (PERV) Infection after Xenotransplantation?

Combining New Non-Nucleoside Reverse Transcriptase Inhibitors (RTIs) with AZT Results in Strong Synergism against Multi-RTI-Resistant HIV-1 Strains

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