ArticleMicrobiology spectrum2022
Combinations of Host- and Virus-Targeting Antiviral Drugs Confer Synergistic Suppression of SARS-CoV-2.
Article in Microbiology spectrum, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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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.
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Who cites it
34 citing papers in PubMed, 55 citations in OpenAlex.
- Host nucleolin-targeting unique peptide drugs as potent broad-spectrum anti-influenza therapies.PNAS nexus · 2026Article
- The Combination of Nirmatrelvir and Ivermectin Exerts Strongly Synergistic Antiviral and Anti-Inflammatory Effects Against Murine Coronavirus Infection of Macrophages.International journal of molecular sciences · 2026Article
- Deadbolt Drug Discovery: Locking the Door to Class 1 Viral Entry by Small Molecules.ACS infectious diseases · 2026Review
- Drug combination treatment as a strategy for inhibiting human adenovirus replication.Antiviral research · 2026Article
- Synergistic antiviral effects of structure-guided peptides and a mutagenic base analog on SARS-CoV-2 replication.Antimicrobial agents and chemotherapy · 2026Article
- Targeting SARS-CoV-2 Non-Structural Proteins: A Blueprint for Next-Generation Small-Molecule Coronavirus Antivirals.Pharmaceutics · 2026Review
- Clinical trial simulation of antiviral drugs.Journal of virology · 2026Review
- PotentJournal of virology · 2026Article
- Evaluation of the efficiency of combined antiviral therapy in COVID-19 challenging immunocompromised patients.Scientific reports · 2026Article
- Model-informed prediction of antiviral drug combination synergy from sparse data using complementary mechanistic and pharmacodynamic approaches.Frontiers in pharmacology · 2026Article
- DABPU-DE targeting host adipose triglyceride lipase provides broad-spectrum anti-coronavirus effectsFrontiers in pharmacology · 2026Article
- Influenza H5Nx viruses are susceptible to MEK1/2 inhibition by zapnometinib.Emerging microbes & infections · 2025Article
- Article
- Prospects of Innovative Therapeutics in Combating the COVID-19 Pandemic.Molecular biotechnology · 2025Review
- Strategies and efforts in circumventing the emergence of antiviral resistance against conventional antivirals.npj antimicrobials and resistance · 2025Review
- Papaverine Targets STAT Signaling: A Dual-Action Therapy Option Against SARS-CoV-2.Journal of medical virology · 2025Article
- Combinations of approved oral nucleoside analogues confer potent suppression of alphavirusesbioRxiv : the preprint server for biology · 2025Article
- Structure-Based Optimization of Pyridone α-Ketoamides as Inhibitors of the SARS-CoV-2 Main Protease.Journal of medicinal chemistry · 2025Article
- Inhaled Dry Powder of Antiviral Agents: A Promising Approach to Treating Respiratory Viral Pathogens.Viruses · 2025Review
- Integrated Analysis of Remdesivir and Paxlovid in COVID-19 Patients: A Personalized Approach to High-Risk Individuals for Severe Evolution.Journal of clinical medicine · 2024Article
Corrections and comments
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Authors and funding
13 authors at 7 institutions in 4 countries.
Funding
Abstract
Three directly acting antivirals (DAAs) demonstrated substantial reduction in COVID-19 hospitalizations and deaths in clinical trials. However, these agents did not completely prevent severe illness and are associated with cases of rebound illness and viral shedding. Combination regimens can enhance antiviral potency, reduce the emergence of drug-resistant variants, and lower the dose of each component in the combination. Concurrently targeting virus entry and virus replication offers opportunities to discover synergistic drug combinations. While combination antiviral drug treatments are standard for chronic RNA virus infections, no antiviral combination therapy has been approved for SARS-CoV-2. Here, we demonstrate that combining host-targeting antivirals (HTAs) that target TMPRSS2 and hence SARS-CoV-2 entry, with the DAA molnupiravir, which targets SARS-CoV-2 replication, synergistically suppresses SARS-CoV-2 infection in Calu-3 lung epithelial cells. Strong synergy was observed when molnupiravir, an oral drug, was combined with three TMPRSS2 (HTA) oral or inhaled inhibitors: camostat, avoralstat, or nafamostat. The combination of camostat plus molnupiravir was also effective against the beta and delta variants of concern. The pyrimidine biosynthesis inhibitor brequinar combined with molnupiravir also conferred robust synergistic inhibition. These HTA+DAA combinations had similar potency to the synergistic all-DAA combination of molnupiravir plus nirmatrelvir, the protease inhibitor found in paxlovid. Pharmacodynamic modeling allowed estimates of antiviral potency at all possible concentrations of each agent within plausible therapeutic ranges, suggesting possible
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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.