ArticleScientific reports2022
Discovery of SARS-CoV-2 antiviral synergy between remdesivir and approved drugs in human lung cells.
Article in Scientific reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 25 citations in OpenAlex.
- Genome-scale metabolic modeling reveals SARS-CoV-2-induced metabolic changes and antiviral targets.Molecular systems biology · 2021Pooled it
- Localized heme sensing through a ternary molecular glue.bioRxiv : the preprint server for biology · 2026Article
- Unlocking the potential of remdesivir: innovative approaches to drug delivery.Drug delivery and translational research · 2025Review
- Antiviral Activity of Medicinal Plant ExtractsPathogens (Basel, Switzerland) · 2025Article
- EfficientAntimicrobial agents and chemotherapy · 2025Article
- Repurposing Drugs and Synergistic Combinations as Potential Therapies for Inhibiting SARS-CoV-2 and Coronavirus Replication.ACS pharmacology & translational science · 2024Article
- Article
- A universal fluorescence polarization high throughput screening assay to target the SAM-binding sites of SARS-CoV-2 and other viral methyltransferases.Emerging microbes & infections · 2023Article
- Repurposing clinically available drugs and therapies for pathogenic targets to combat SARS-CoV-2.MedComm · 2023Review
- Combinations of Host- and Virus-Targeting Antiviral Drugs Confer Synergistic Suppression of SARS-CoV-2.Microbiology spectrum · 2022Article
- Artificial Neural Network-Based Study Predicts GS-441524 as a Potential Inhibitor of SARS-CoV-2 Activator Protein Furin: a Polypharmacology Approach.Applied biochemistry and biotechnology · 2022Article
- Identifying Structural Features of Nucleotide Analogues to Overcome SARS-CoV-2 Exonuclease Activity.Viruses · 2022Article
- Broad-spectrum CRISPR-mediated inhibition of SARS-CoV-2 variants and endemic coronaviruses in vitro.Nature communications · 2022Article
- Efficacy and safety of the sofosbuvir/velpatasvir combination for the treatment of patients with early mild to moderate COVID-19.Scientific reports · 2022Article
- Combination of antiviral drugs inhibits SARS-CoV-2 polymerase and exonuclease and demonstrates COVID-19 therapeutic potential in viral cell culture.Communications biology · 2022Article
- Anti-Fungal Drug Anidulafungin Inhibits SARS-CoV-2 Spike-Induced Syncytia Formation by Targeting ACE2-Spike Protein Interaction.Frontiers in genetics · 2022Article
- Drug Combinations as a First Line of Defense against Coronaviruses and Other Emerging Viruses.mBio · 2021Review
- Repurposing of FDA-approved drugs against active site and potential allosteric drug-binding sites of COVID-19 main protease.Proteins · 2021Article
- SARS-CoV-2 nucleocapsid protein forms condensates with viral genomic RNA.PLoS biology · 2021Article
- Genome-scale metabolic modeling reveals SARS-CoV-2-induced metabolic changes and antiviral targets.bioRxiv : the preprint server for biology · 2021Article
Corrections and comments
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Authors and funding
23 authors at 6 institutions in 1 country.
Funding
Abstract
SARS coronavirus 2 (SARS-CoV-2) has caused an ongoing global pandemic with significant mortality and morbidity. At this time, the only FDA-approved therapeutic for COVID-19 is remdesivir, a broad-spectrum antiviral nucleoside analog. Efficacy is only moderate, and improved treatment strategies are urgently needed. To accomplish this goal, we devised a strategy to identify compounds that act synergistically with remdesivir in preventing SARS-CoV-2 replication. We conducted combinatorial high-throughput screening in the presence of submaximal remdesivir concentrations, using a human lung epithelial cell line infected with a clinical isolate of SARS-CoV-2. This identified 20 approved drugs that act synergistically with remdesivir, many with favorable pharmacokinetic and safety profiles. Strongest effects were observed with established antivirals, Hepatitis C virus nonstructural protein 5A (HCV NS5A) inhibitors velpatasvir and elbasvir. Combination with their partner drugs sofosbuvir and grazoprevir further increased efficacy, increasing remdesivir's apparent potency > 25-fold. We report that HCV NS5A inhibitors act on the SARS-CoV-2 exonuclease proofreader, providing a possible explanation for the synergy observed with nucleoside analog remdesivir. FDA-approved Hepatitis C therapeutics Epclusa® (velpatasvir/sofosbuvir) and Zepatier® (elbasvir/grazoprevir) could be further optimized to achieve potency and pharmacokinetic properties that support clinical evaluation in combination with remdesivir.
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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.