ArticleJournal of proteome research2020
Nucleotide Analogues as Inhibitors of SARS-CoV-2 Polymerase, a Key Drug Target for COVID-19.
Article in Journal of proteome research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 175 papers, 3 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
175 citing papers in PubMed, 3 syntheses or guidelines pooled it, 287 citations in OpenAlex.
- Efficacy of tenofovir on clinical outcomes of COVID-19 patients: a systematic review.BMC infectious diseases · 2025Pooled it
- Efficacy of antiviral therapies for COVID-19: a systematic review of randomized controlled trials.BMC infectious diseases · 2022Pooled it
- Sofosbuvir/daclatasvir regimens for the treatment of COVID-19: an individual patient data meta-analysis.The Journal of antimicrobial chemotherapy · 2021Pooled it
- A randomized, double-blind, placebo-controlled trial of IL-7 in critically ill patients with COVID-19.JCI insight · 2025Trial
- Daily tenofovir disoproxil fumarate/emtricitabine and hydroxychloroquine for pre-exposure prophylaxis of COVID-19: a double-blind placebo-controlled randomized trial in healthcare workers.Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases · 2023Trial
- Efficacy and safety of sofosbuvir plus daclatasvir or ravidasvir in patients with COVID-19: A randomized controlled trial.Journal of medical virology · 2021Trial
- The impact of sofosbuvir/daclatasvir or ribavirin in patients with severe COVID-19.The Journal of antimicrobial chemotherapy · 2020Trial
- Sofosbuvir and daclatasvir compared with standard of care in the treatment of patients admitted to hospital with moderate or severe coronavirus infection (COVID-19): a randomized controlled trial.The Journal of antimicrobial chemotherapy · 2020Trial
- Evaluation of the efficacy of sofosbuvir plus daclatasvir in combination with ribavirin for hospitalized COVID-19 patients with moderate disease compared with standard care: a single-centre, randomized controlled trial.The Journal of antimicrobial chemotherapy · 2020Trial
- Copy-back RNA synthesis by coronavirus polymerase requires helicase activity and is stimulated by remdesivir and molnupiravir.Science advances · 2026Article
- RNA with Azvudine Incorporated One Nucleotide Upstream of 3'-End Resists Cleavage by SARS-CoV-2 Proofreading Exonuclease.Research square · 2026Article
- PrEPped for COVID? The association between HIV-PrEP use and COVID-19 among men and gender diverse people who have sex with men: findings from three large online surveys in the United Kingdom.BMC public health · 2026Article
- Mechanism of SARS-CoV-2 resistance to nucleotide analog-based antivirals.Nature communications · 2026Article
- Article
- Tenofovir attenuates cytokine storm and bronchiolar damage in a mouse model of bleomycin-induced acute lung injury.Scientific reports · 2025Article
- Viral Reprogramming of Nucleotide Synthesis and Its Impact on Viral Infection.Journal of medical virology · 2025Review
- A post-assembly conformational change makes the SARS-CoV-2 polymerase elongation-competent.Nucleic acids research · 2025Article
- Exploring the Therapeutic Potential ofJournal of microbiology and biotechnology · 2025Article
- SARS-CoV-2 drug resistance and therapeutic approaches.Heliyon · 2025Review
- Optimization of a micro-scale air-liquid-interface model of human proximal airway epithelium for moderate throughput drug screening for SARS-CoV-2.Respiratory research · 2025Article
115 more citing papers are in PubMed but not listed here.
Corrections and comments
- Update of
Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
SARS-CoV-2 is responsible for the current COVID-19 pandemic. On the basis of our analysis of hepatitis C virus and coronavirus replication, and the molecular structures and activities of viral inhibitors, we previously demonstrated that three nucleotide analogues (the triphosphates of Sofosbuvir, Alovudine, and AZT) inhibit the SARS-CoV RNA-dependent RNA polymerase (RdRp). We also demonstrated that a library of additional nucleotide analogues terminate RNA synthesis catalyzed by the SARS-CoV-2 RdRp, a well-established drug target for COVID-19. Here, we used polymerase extension experiments to demonstrate that the active triphosphate form of Sofosbuvir (an FDA-approved hepatitis C drug) is incorporated by SARS-CoV-2 RdRp and blocks further incorporation. Using the molecular insight gained from the previous studies, we selected the active triphosphate forms of six other antiviral agents, Alovudine, Tenofovir alafenamide, AZT, Abacavir, Lamivudine, and Emtricitabine, for evaluation as inhibitors of the SARS-CoV-2 RdRp and demonstrated the ability of these viral polymerase inhibitors to be incorporated by SARS-CoV-2 RdRp, where they terminate further polymerase extension with varying efficiency. These results provide a molecular basis for inhibition of the SARS-CoV-2 RdRp by these nucleotide analogues. If sufficient efficacy of some of these FDA-approved drugs in inhibiting viral replication in cell culture is established, they may be explored as potential COVID-19 therapeutics.
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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.