ArticleInnovation (Cambridge (Mass.))2021
Structural Basis of SARS-CoV-2 Polymerase Inhibition by Favipiravir.
Article in Innovation (Cambridge (Mass.)), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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Who cites it
61 citing papers in PubMed, 85 citations in OpenAlex.
- Structural and functional characterisation of the Crimean-Congo haemorrhagic fever virus RNA dependent RNA polymerase.Nature communications · 2026Article
- Pharmacokinetic Assessment of Atazanavir and Favipiravir Following Echinacea Supplementation: A Controlled Herb-Drug Interaction Investigation.Biopharmaceutics & drug disposition · 2026Article
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- Investigation of the functional hot-spot residues of an enzyme by real-time monitoring of the enzymatic reaction using NMR and computational approaches.Scientific reports · 2026Article
- SARS-CoV-2 Remdesivir Exposure Leads to Different Evolutionary Pathways That Converge in Moderate Levels of Drug Resistance.Viruses · 2025Article
- Strategies and efforts in circumventing the emergence of antiviral resistance against conventional antivirals.npj antimicrobials and resistance · 2025Review
- Review
- Observational
- Drupacine as a potent SARS-CoV-2 replication inhibitorBiosafety and health · 2024Article
- Cryo-EM structure of DNA polymerase of African swine fever virus.Nucleic acids research · 2024Article
- Small Molecule Drugs Targeting Viral Polymerases.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Favipiravir, an antiviral drug, in combination with tamoxifen exerts synergistic effect in tamoxifen-resistant breast cancer cells via hTERT inhibition.Scientific reports · 2024Article
- Favipiravir Analogues as Inhibitors of SARS-CoV-2 RNA-Dependent RNA Polymerase, Combined Quantum Chemical Modeling, Quantitative Structure-Property Relationship, and Molecular Docking Study.Molecules (Basel, Switzerland) · 2024Article
- Viral replication organelles: the highly complex and programmed replication machinery.Frontiers in microbiology · 2024Review
- Inhibition of the RNA-Dependent RNA-Polymerase from SARS-CoV-2 by 6-Chloropurine Isoxazoline-Carbocyclic Monophosphate Nucleotides.ACS omega · 2023Article
- Article
- COVID-19 therapeutics: Clinical application of repurposed drugs and futuristic strategies for target-based drug discovery.Genes & diseases · 2023Review
- Hydrogen Bonding (Base Pairing) in Antiviral Activity.Viruses · 2023Article
- Elucidating the Role of Noncovalent Interactions in Favipiravir, a Drug Active against Various Human RNA Viruses; aMolecules (Basel, Switzerland) · 2023Article
- Kill or corrupt: Mechanisms of action and drug-resistance of nucleotide analogues against SARS-CoV-2.Antiviral research · 2023Review
1 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has developed into an unprecedented global pandemic. Nucleoside analogs, such as Remdesivir and Favipiravir, can serve as the first-line broad-spectrum antiviral drugs by targeting the viral polymerases. However, the underlying mechanisms for the antiviral efficacies of these drugs are far from well understood. Here, we reveal that Favipiravir, as a pyrazine derivative, could be incorporated into the viral RNA products by mimicking both adenine and guanine nucleotides. This drug thus inhibits viral replication mainly by inducing mutations in progeny RNAs, different from Remdesivir or other RNA-terminating nucleoside analogs that impair the elongation of RNA products. We further determined the cryo-EM structure of Favipiravir bound to the replicating polymerase complex of SARS-CoV-2 in the pre-catalytic state. This structure provides a missing snapshot for visualizing the catalysis dynamics of coronavirus polymerase, and reveals an unexpected base-pairing pattern between Favipiravir and pyrimidine residues that may explain its capacity for mimicking both adenine and guanine nucleotides. These findings shed light on the mechanism of coronavirus polymerase catalysis and provide a rational basis for developing antiviral drugs to combat the SARS-CoV-2 pandemic.
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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.