ArticleCommunications biology2022
Combination of antiviral drugs inhibits SARS-CoV-2 polymerase and exonuclease and demonstrates COVID-19 therapeutic potential in viral cell culture.
Article in Communications biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 70 citations in OpenAlex.
- Special Issue "Antiviral Drugs Discovery".International journal of molecular sciences · 2026Article
- Coronavirus Nsp15 endoribonuclease: linking viral RNA regulation to immune evasion and viral fitness.Journal of virology · 2026Review
- Novel Mechanisms of SARS-CoV-2 Drug Resistance and Rational Design of Anti-Resistant Antivirals.Molecules (Basel, Switzerland) · 2026Article
- 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
- An Anti-HIV Drug Is Highly Effective Against SARS-CoV-2 In Vitro and Has Potential Benefit for Long COVID Treatment.Viruses · 2025Article
- Construction and validation of a cell based reporter assay for identifying inhibitors of SARS coronavirus 2 RNA dependent RNA polymerase activity.Scientific reports · 2025Article
- A High-Throughput Screening Pipeline to Identify Methyltransferase and Exonuclease Inhibitors of SARS-CoV-2 NSP14.Biochemistry · 2025Article
- Repurposing of lonafarnib as a treatment for SARS-CoV-2 infection.JCI insight · 2025Article
- The comprehensive SARS-CoV-2 'hijackome' knowledge base.Cell discovery · 2024Article
- Biochemical simulation of mutation synthesis and repair during SARS-CoV-2 RNA polymerization.Virology · 2024Article
- Newly Proposed Dose of Daclatasvir to Prevent Lethal SARS-CoV-2 Infection in Human Transgenic ACE-2 Mice.Viruses · 2024Article
- Multidrug Combinations against SARS-CoV-2 Using GS-441524 or Ivermectin with Molnupiravir and/or Nirmatrelvir in Reconstituted Human Nasal Airway Epithelia.Pharmaceutics · 2024Article
- SARS-CoV-2 papain-like protease inhibits ISGylation of the viral nucleocapsid protein to evade host anti-viral immunity.Journal of virology · 2024Article
- COVID-19 drug discovery and treatment options.Nature reviews. Microbiology · 2024Review
- Article
- A Narrative Overview of Coronavirus Infection: Clinical Signs and Symptoms, Viral Entry and Replication, Treatment Modalities, and Management.Current topics in medicinal chemistry · 2024Review
- Specific binding of G-quadruplex in SARS-CoV-2 RNA by RHAU peptide.Current research in structural biology · 2024Article
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Authors and funding
19 authors at 4 institutions in 2 countries.
Funding
Abstract
SARS-CoV-2 has an exonuclease-based proofreader, which removes nucleotide inhibitors such as Remdesivir that are incorporated into the viral RNA during replication, reducing the efficacy of these drugs for treating COVID-19. Combinations of inhibitors of both the viral RNA-dependent RNA polymerase and the exonuclease could overcome this deficiency. Here we report the identification of hepatitis C virus NS5A inhibitors Pibrentasvir and Ombitasvir as SARS-CoV-2 exonuclease inhibitors. In the presence of Pibrentasvir, RNAs terminated with the active forms of the prodrugs Sofosbuvir, Remdesivir, Favipiravir, Molnupiravir and AT-527 were largely protected from excision by the exonuclease, while in the absence of Pibrentasvir, there was rapid excision. Due to its unique structure, Tenofovir-terminated RNA was highly resistant to exonuclease excision even in the absence of Pibrentasvir. Viral cell culture studies also demonstrate significant synergy using this combination strategy. This study supports the use of combination drugs that inhibit both the SARS-CoV-2 polymerase and exonuclease for effective COVID-19 treatment.
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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.