ArticleThe Journal of biological chemistry2011
Mechanism of HIV reverse transcriptase inhibition by zinc: formation of a highly stable enzyme-(primer-template) complex with profoundly diminished catalytic activity.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
35 citing papers in PubMed, 51 citations in OpenAlex.
- First-in-Human Trial of MIV-150 and Zinc Acetate Coformulated in a Carrageenan Gel: Safety, Pharmacokinetics, Acceptability, Adherence, and Pharmacodynamics.Journal of acquired immune deficiency syndromes (1999) · 2016Trial
- ROS-mitochondria-NLRP3/STING axis mediates the enhanced anti-coronavirus activity of ZIF8 nanoparticles.Journal of nanobiotechnology · 2026Article
- Pharmacophores of Influenza Virus PA Endonuclease Inhibitors.Advances in experimental medicine and biology · 2026Review
- Antiviral potential of zinc ion: mechanisms and applications in viral infections.Frontiers in microbiology · 2026Review
- Targeted Application of Functional Foods as Immune Fitness Boosters in the Defense against Viral Infection.Nutrients · 2023Review
- Antiviral activity of zinc against hepatitis viruses: current status and future prospects.Frontiers in microbiology · 2023Review
- Orsay Virus Infection of Caenorhabditis elegans Is Modulated by Zinc and Dependent on Lipids.Journal of virology · 2022Article
- The Zinc Content of HIV-1 NCp7 Affects Its Selectivity for Packaging Signal and Affinity for Stem-Loop 3.Viruses · 2021Article
- Zinc: Multidimensional Effects on Living Organisms.Biomedicines · 2021Review
- Aristocratic human papillomavirus drove cervical cancer: a study of the therapeutic potential of the combination of interferon with zinc.Molecular and cellular biochemistry · 2021Review
- Potential health benefits of zinc supplementation for the management of COVID-19 pandemic.Journal of food biochemistry · 2021Review
- Zinc Influx Restricts Enterovirus D68 Replication.Frontiers in microbiology · 2021Article
- Retroviral RNase H: Structure, mechanism, and inhibition.The Enzymes · 2021Review
- Structural basis for CaBiophysics and physicobiology · 2021Article
- Medicinal Plants and Zinc: Impact on COVID-19 Pandemic.TheScientificWorldJournal · 2021Review
- Article
- Review
- Determinants of Active-Site Inhibitor Interaction with HIV-1 RNase H.ACS infectious diseases · 2019Article
- The Role of Zinc in Antiviral Immunity.Advances in nutrition (Bethesda, Md.) · 2019Review
- Non-nucleoside Reverse Transcriptase Inhibitors Inhibit Reverse Transcriptase through a Mutually Exclusive Interaction with Divalent Cation-dNTP Complexes.Biochemistry · 2019Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Several physiologically relevant cations including Ca(2+), Mn(2+), and Zn(2+) have been shown to inhibit HIV reverse transcriptase (RT), presumably by competitively displacing one or more Mg(2+) ions bound to RT. We analyzed the effects of Zn(2+) on reverse transcription and compared them to Ca(2+) and Mn(2+). Using nucleotide extension efficiency as a readout, Zn(2+) showed significant inhibition of reactions with 2 mM Mg(2+), even when present at only ∼5 μM. Mn(2+) and Ca(2+) were also inhibitory but at higher concentrations. Both Mn(2+) and Zn(2+) (but not Ca(2+)) supported RT incorporation in the absence of Mg(2+) with Mn(2+) being much more efficient. The maximum extension rates with Zn(2+), Mn(2+), and Mg(2+) were ∼0.1, 1, and 3.5 nucleotides per second, respectively. Zinc supported optimal RNase H activity at ∼25 μM, similar to the optimal for nucleotide addition in the presence of low dNTP concentrations. Surprisingly, processivity (average number of nucleotides incorporated in a single binding event with enzyme) during reverse transcription was comparable with Zn(2+) and Mg(2+), and single RT molecules were able to continue extension in the presence of Zn(2+) for several hours on the same template. Consistent with this result, the half-life for RT-Zn(2+)-(primer-template) complexes was 220 ± 60 min and only 1.7 ± 1 min with Mg(2+), indicating ∼130-fold more stable binding with Zn(2+). Essentially, the presence of Zn(2+) promotes the formation of a highly stable slowly progressing RT-(primer-template) complex.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.