ArticleScientific reports2020
Sofosbuvir terminated RNA is more resistant to SARS-CoV-2 proofreader than RNA terminated by Remdesivir.
Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
59 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Comparative effectiveness of pharmacological interventions on mortality and the average length of hospital stay of patients with COVID-19: a systematic review and meta-analysis of randomized controlled trials.Expert review of anti-infective therapy · 2022Pooled it
- Sofosbuvir/ledipasvir in combination or nitazoxanide alone are safe and efficient treatments for COVID-19 infection: A randomized controlled trial for repurposing antivirals.Arab journal of gastroenterology : the official publication of the Pan-Arab Association of Gastroenterology · 2022Trial
- Review on drug repositioning of some FDA-approved drugs for treatment of cancer/microbial diseases.RSC advances · 2026Review
- RNA with Azvudine Incorporated One Nucleotide Upstream of 3'-End Resists Cleavage by SARS-CoV-2 Proofreading Exonuclease.Research square · 2026Article
- Mechanism of SARS-CoV-2 resistance to nucleotide analog-based antivirals.Nature communications · 2026Article
- Biochemical simulation of mutation synthesis and repair during SARS-CoV-2 RNA polymerization.Virology · 2024Article
- An Overview of SARS-CoV-2 Potential Targets, Inhibitors, and Computational Insights to Enrich the Promising Treatment Strategies.Current microbiology · 2024Review
- Why Certain Repurposed Drugs Are Unlikely to Be Effective Antivirals to Treat SARS-CoV-2 Infections.Viruses · 2024Article
- Evaluating the Therapeutic Effect of Sofosbuvir in Outpatients with COVID-19: A Randomized Clinical Trial Study.Galen medical journal · 2024Article
- Patients with Hepatitis C Undergoing Direct-Acting Antiviral Treatment Have a Lower SARS-CoV-2 Infection Rate.Life (Basel, Switzerland) · 2023Article
- Review
- COVID-19 therapeutics: Clinical application of repurposed drugs and futuristic strategies for target-based drug discovery.Genes & diseases · 2023Review
- Structure-Based Drug Design of RdRp Inhibitors against SARS-CoV-2.Topics in current chemistry (Cham) · 2023Review
- COVID-19 Therapeutic Potential of Natural Products.International journal of molecular sciences · 2023Review
- Comparative study of four innovative earth-friendly platforms for rapid analysis of daclatasvir dihydrochloride: Application on different matrices.BMC chemistry · 2023Article
- Preclinical development of kinetin as a safe error-prone SARS-CoV-2 antiviral able to attenuate virus-induced inflammation.Nature communications · 2023Article
- A review on structural, non-structural, and accessory proteins of SARS-CoV-2: Highlighting drug target sites.Immunobiology · 2023Review
- Current understanding of nucleoside analogs inhibiting the SARS-CoV-2 RNA-dependent RNA polymerase.Computational and structural biotechnology journal · 2023Review
- Discovering new potential inhibitors to SARS-CoV-2 RNA dependent RNA polymerase (RdRp) using high throughput virtual screening and molecular dynamics simulations.Scientific reports · 2022Article
- Discovery of SARS-CoV-2 antiviral synergy between remdesivir and approved drugs in human lung cells.Scientific reports · 2022Article
Corrections and comments
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Authors and funding
9 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
SARS-CoV-2 is responsible for COVID-19, resulting in the largest pandemic in over a hundred years. After examining the molecular structures and activities of hepatitis C viral inhibitors and comparing hepatitis C virus and coronavirus replication, we previously postulated that the FDA-approved hepatitis C drug EPCLUSA (Sofosbuvir/Velpatasvir) might inhibit SARS-CoV-2. We subsequently demonstrated that Sofosbuvir triphosphate is incorporated by the relatively low fidelity SARS-CoV and SARS-CoV-2 RNA-dependent RNA polymerases (RdRps), serving as an immediate polymerase reaction terminator, but not by a host-like high fidelity DNA polymerase. Other investigators have since demonstrated the ability of Sofosbuvir to inhibit SARS-CoV-2 replication in lung and brain cells; additionally, COVID-19 clinical trials with EPCLUSA and with Sofosbuvir plus Daclatasvir have been initiated in several countries. SARS-CoV-2 has an exonuclease-based proofreader to maintain the viral genome integrity. Any effective antiviral targeting the SARS-CoV-2 RdRp must display a certain level of resistance to this proofreading activity. We report here that Sofosbuvir terminated RNA resists removal by the exonuclease to a substantially higher extent than RNA terminated by Remdesivir, another drug being used as a COVID-19 therapeutic. These results offer a molecular basis supporting the current use of Sofosbuvir in combination with other drugs in COVID-19 clinical trials.
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