ArticleScience translational medicine2016
Mathematical modeling of herpes simplex virus-2 suppression with pritelivir predicts trial outcomes.
Article in Science translational medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.
What it found
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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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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Optimizing clinical dosing of combination broadly neutralizing antibodies for HIV prevention.PLoS computational biology · 2022Pooled it
- Mathematical Modeling of Within-Host, Untreated, Cytomegalovirus Infection Dynamics after Allogeneic Transplantation.Viruses · 2021Trial
- Clinical trial simulation of antiviral drugs.Journal of virology · 2026Review
- Review
- Spatially structured models of viral dynamics: a scoping review.Microbiology and molecular biology reviews : MMBR · 2025Article
- Human Herpes Virus-8 Oral Shedding Heterogeneity Is Due to Varying Rates of Reactivation from Latency and Immune Containment.Viruses · 2025Article
- Intracellular and extracellular dynamics of herpes simplex virus 1 DNA and infectious particles in epithelial and neuronal cells.bioRxiv : the preprint server for biology · 2025Article
- Modeling the Impact of Ensitrelvir on SARS-CoV-2 Dynamics and Its Application for Assessment of Transmission Mitigation of Patients with COVID-19.Infectious diseases and therapy · 2024Article
- A unifying model to explain frequent SARS-CoV-2 rebound after nirmatrelvir treatment and limited prophylactic efficacy.Nature communications · 2024Article
- A unifying model to explain high nirmatrelvir therapeutic efficacy against SARS-CoV-2, despite low post-exposure prophylaxis efficacy and frequent viral rebound.medRxiv : the preprint server for health sciences · 2024Article
- Heterogeneous SARS-CoV-2 kinetics due to variable timing and intensity of immune responses.JCI insight · 2024Article
- Two-way pharmacodynamic modeling of drug combinations and its application to pairs of repurposed Ebola and SARS-CoV-2 agents.Antimicrobial agents and chemotherapy · 2024Article
- Heterogeneous SARS-CoV-2 kinetics due to variable timing and intensity of immune responses.medRxiv : the preprint server for health sciences · 2024Article
- Review
- The risk of drug resistance during long-acting antimicrobial therapy.Proceedings. Biological sciences · 2022Article
- Modeling explains prolonged SARS-CoV-2 nasal shedding relative to lung shedding in remdesivir-treated rhesus macaques.iScience · 2022Article
- 40 Years after the Registration of Acyclovir: Do We Need New Anti-Herpetic Drugs?International journal of molecular sciences · 2022Review
- Estimation of the in vivo neutralization potency of eCD4Ig and conditions for AAV-mediated production for SHIV long-term remission.Science advances · 2022Article
- Drug Combinations as a First Line of Defense against Coronaviruses and Other Emerging Viruses.mBio · 2021Review
- Hybrid computational modeling demonstrates the utility of simulating complex cellular networks in type 1 diabetes.PLoS computational biology · 2021Article
Corrections and comments
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Authors and funding
14 authors.
Funding
Abstract
Pharmacokinetic and pharmacodynamic models estimate the potency of antiviral agents but do not capture viral and immunologic factors that drive the natural dynamics of infection. We designed a mathematical model that synthesizes pharmacokinetics, pharmacodynamics, and viral pathogenesis concepts to simulate the activity of pritelivir, a DNA helicase-primase inhibitor that targets herpes simplex virus. Our simulations recapitulate detailed viral kinetic shedding features in five dosage arms of a phase 2 clinical trial. We identify that in vitro estimates of median effective concentration (EC50) are lower than in vivo values for the drug. Nevertheless, pritelivir potently decreases shedding at appropriate doses based on its mode of action and long half-life. Although pritelivir directly inhibits replication in epithelial cells, our model indicates that pritelivir also indirectly limits downstream viral spread from neurons to genital keratinocytes, within genital ulcers, and from ulcer to new mucosal sites of infection. We validate our model based on its ability to predict outcomes in a subsequent trial with a higher dose. The model can therefore be used to optimize dose selection in clinical practice.
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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.