Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.49 (reverse transcriptase)
 31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human Immunodeficiency Virus replication offers several targets for inhibitory compounds, the foremost presently being the HIV reverse transcriptase. Since the beginning of the epidemic three nucleoside analogue drugs--Zidovudine, Didanosine and Zalcitabine--which act at the reverse transcriptase enzyme are already licensed for use in AIDS-therapy, and others--Stavudine, Alovudine and Lamivudine--are still under clinical evaluation. Although there is a very significant research work for newer drugs for HIV-therapy, it seems that for the next future Zidovudine will remain the most important drug of antiretroviral therapy.
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PMID:[Future possibilities of drug therapy of acquired immunodeficiency syndrome]. 801 18

Several new nucleoside analogs are currently in development for the treatment of HIV-1 infections. Alovudine, amdoxovir, elvucitabine, Racivir, Reverset and SPD 754 are nucleoside reverse transcriptase inhibitors that were designed and selected in anticipation of having improved resistance, safety, compatibility and efficacy profiles. Clinical trials are demonstrating that some of these goals are being met, and that nucleoside analogs as a class of compounds remain fertile ground for finding valuable additions to current anti-retrovirus treatment regimens.
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PMID:New nucleoside reverse transcriptase inhibitors for the treatment of HIV infections. 1535 46

SARS-CoV-2, a member of the coronavirus family, has caused a global public health emergency. Based on our analysis of hepatitis C virus and coronavirus replication, and the molecular structures and activities of viral inhibitors, we previously reasoned that the FDA-approved hepatitis C drug EPCLUSA (Sofosbuvir/Velpatasvir) should inhibit coronaviruses, including SARS-CoV-2. Here, using model polymerase extension experiments, we demonstrate that the active triphosphate form of Sofosbuvir is incorporated by low-fidelity polymerases and SARS-CoV RNA-dependent RNA polymerase (RdRp), and blocks further incorporation by these polymerases; the active triphosphate form of Sofosbuvir is not incorporated by a host-like high-fidelity DNA polymerase. Using the same molecular insight, we selected 3'-fluoro-3'-deoxythymidine triphosphate and 3'-azido-3'-deoxythymidine triphosphate, which are the active forms of two other anti-viral agents, Alovudine and AZT (an FDA-approved HIV/AIDS drug) for evaluation as inhibitors of SARS-CoV RdRp. We demonstrate the ability of two of these HIV reverse transcriptase inhibitors to be incorporated by SARS-CoV RdRp where they also terminate further polymerase extension. Given the 98% amino acid similarity of the SARS-CoV and SARS-CoV-2 RdRps, we expect these nucleotide analogues would also inhibit the SARS-CoV-2 polymerase. These results offer guidance to further modify these nucleotide analogues to generate more potent broad-spectrum anti-coronavirus agents.
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PMID:Nucleotide analogues as inhibitors of SARS-CoV Polymerase. 3312 86