ArticleProceedings of the National Academy of Sciences of the United States of America2017
Quantifying antiviral activity optimizes drug combinations against hepatitis C virus infection.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed.
- Clinical trial simulation of antiviral drugs.Journal of virology · 2026Review
- Mathematical Modeling of Virus-Mediated Syncytia Formation: Past Successes and Future Directions.Results and problems in cell differentiation · 2024Review
- A viral RNA-dependent RNA polymerase inhibitor VV116 broadly inhibits human coronaviruses and has synergistic potency with 3CLpro inhibitor nirmatrelvir.Signal transduction and targeted therapy · 2023Article
- Potential Anti-Mpox Virus Activity of Atovaquone, Mefloquine, and Molnupiravir, and Their Potential Use as Treatments.The Journal of infectious diseases · 2023Article
- Different efficacies of neutralizing antibodies and antiviral drugs on SARS-CoV-2 Omicron subvariants, BA.1 and BA.2.Antiviral research · 2022Article
- Treatment of Respiratory Viral Coinfections.Epidemiologia (Basel, Switzerland) · 2022Article
- Comparative highlights on MERS-CoV, SARS-CoV-1, SARS-CoV-2, and NEO-CoV.EXCLI journal · 2022Review
- Preclinical characterization of an intravenous coronavirus 3CL protease inhibitor for the potential treatment of COVID19.Nature communications · 2021Article
- Drugs repurposed for COVID-19 by virtual screening of 6,218 drugs and cell-based assay.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- A quantitative model used to compare within-host SARS-CoV-2, MERS-CoV, and SARS-CoV dynamics provides insights into the pathogenesis and treatment of SARS-CoV-2.PLoS biology · 2021Article
- Low Inducibility of Latent Human Immunodeficiency Virus Type 1 Proviruses as a Major Barrier to Cure.The Journal of infectious diseases · 2021Review
- Mefloquine, a Potent Anti-severe Acute Respiratory Syndrome-Related Coronavirus 2 (SARS-CoV-2) Drug as an Entry InhibitorFrontiers in microbiology · 2021Article
- Strategy, Progress, and Challenges of Drug Repurposing for Efficient Antiviral Discovery.Frontiers in pharmacology · 2021Review
- Janus Dendrimers to Assess the Anti-HCV Activity of Molecules in Cell-Assays.Pharmaceutics · 2020Article
- Article
- Modeling Favipiravir Antiviral Efficacy Against Emerging Viruses: From Animal Studies to Clinical Trials.CPT: pharmacometrics & systems pharmacology · 2020Review
- Danoprevir for the Treatment of Hepatitis C Virus Infection: Design, Development, and Place in Therapy.Drug design, development and therapy · 2020Review
- Mutational pathway maps and founder effects define the within-host spectrum of hepatitis C virus mutants resistant to drugs.PLoS pathogens · 2019Article
- Insight into treatment of HIV infection from viral dynamics models.Immunological reviews · 2018Review
- Interferon at the cellular, individual, and population level in hepatitis C virus infection: Its role in the interferon-free treatment era.Immunological reviews · 2018Review
Corrections and comments
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- Erratum issued
Authors and funding
8 authors.
Funding
Abstract
With the introduction of direct-acting antivirals (DAAs), treatment against hepatitis C virus (HCV) has significantly improved. To manage and control this worldwide infectious disease better, the "best" multidrug treatment is demanded based on scientific evidence. However, there is no method available that systematically quantifies and compares the antiviral efficacy and drug-resistance profiles of drug combinations. Based on experimental anti-HCV profiles in a cell culture system, we quantified the instantaneous inhibitory potential (IIP), which is the logarithm of the reduction in viral replication events, for both single drugs and multiple-drug combinations. From the calculated IIP of 15 anti-HCV drugs from different classes [telaprevir, danoprevir, asunaprevir, simeprevir, sofosbuvir (SOF), VX-222, dasabuvir, nesbuvir, tegobuvir, daclatasvir, ledipasvir, IFN-α, IFN-λ1, cyclosporin A, and SCY-635], we found that the nucleoside polymerase inhibitor SOF had one of the largest potentials to inhibit viral replication events. We also compared intrinsic antiviral activities of a panel of drug combinations. Our quantification analysis clearly indicated an advantage of triple-DAA treatments over double-DAA treatments, with triple-DAA treatments showing enhanced antiviral activity and a significantly lower probability for drug resistance to emerge at clinically relevant drug concentrations. Our framework provides quantitative information to consider in designing multidrug strategies before costly clinical trials.
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