ArticleAntimicrobial agents and chemotherapy2020
The FDA-Approved Drug Nelfinavir Inhibits Lytic Cell-Free but Not Cell-Associated Nonlytic Transmission of Human Adenovirus.
Article in Antimicrobial agents and chemotherapy, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 27 citations in OpenAlex.
- Target-Based Antiviral Drug Development Against Human Respiratory Viruses.Pathogens (Basel, Switzerland) · 2026Review
- Potency-enhancing mutations in E3-19K and i-leader increase the cytolytic activity of the PH20/Molecular therapy. Oncology · 2026Article
- PyPlaque is an open-source python package for phenotypic analysis of virus plaque assays.Scientific reports · 2025Article
- Nonlytic Egress and Transmission in the Virus World.Annual review of biochemistry · 2025Review
- Activated blood-derived human primary T cells support replication of HAdV C5 and virus transmission to polarized human primary epithelial cells.Journal of virology · 2025Article
- Breaking the Chain: Protease Inhibitors as Game Changers in Respiratory Viruses Management.International journal of molecular sciences · 2024Review
- A versatile automated pipeline for quantifying virus infectivity by label-free light microscopy and artificial intelligence.Nature communications · 2024Article
- Current antiviral agents against human adenoviruses associated with respiratory infections.Frontiers in pediatrics · 2024Review
- Selenadiazole Inhibited Adenovirus-Induced Apoptosis through the Oxidative-Damage-Mediated Bcl-2/Stat 3/NF-κB Signaling Pathway.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Adenoviruses in medicine: innocuous pathogen, predator, or partner.Trends in molecular medicine · 2023Review
- Viral proteases as therapeutic targets.Molecular aspects of medicine · 2022Review
- High-content, arrayed compound screens with rhinovirus, influenza A virus and herpes simplex virus infections.Scientific data · 2022Article
- Chemical Evolution of Rhinovirus Identifies Capsid-Destabilizing Mutations Driving Low-pH-Independent Genome Uncoating.Journal of virology · 2022Article
- Identification of broad anti-coronavirus chemical agents for repurposing against SARS-CoV-2 and variants of concern.Current research in virological science · 2022Article
- Human Adenovirus Type 5 Infection Leads to Nuclear Envelope Destabilization and Membrane Permeability Independently of Adenovirus Death Protein.International journal of molecular sciences · 2021Article
- Virus Infection Variability by Single-Cell Profiling.Viruses · 2021Review
- Microscopy deep learning predicts virus infections and reveals mechanics of lytic-infected cells.iScience · 2021Article
- Emerging antiviral therapeutics for human adenovirus infection: Recent developments and novel strategies.Antiviral research · 2021Review
- Recent Advances in Novel Antiviral Therapies against Human Adenovirus.Microorganisms · 2020Review
- A high-content image-based drug screen of clinical compounds against cell transmission of adenovirus.Scientific data · 2020Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Adenoviruses (AdVs) are prevalent and give rise to chronic and recurrent disease. Human AdV (HAdV) species B and C, such as HAdV-C2, -C5, and -B14, cause respiratory disease and constitute a health threat for immunocompromised individuals. HAdV-Cs are well known for lysing cells owing to the E3 CR1-β-encoded adenovirus death protein (ADP). We previously reported a high-throughput image-based screening framework and identified an inhibitor of HAdV-C2 multiround infection, nelfinavir mesylate. Nelfinavir is the active ingredient of Viracept, an FDA-approved inhibitor of human immunodeficiency virus (HIV) aspartyl protease that is used to treat AIDS. It is not effective against single-round HAdV infections. Here, we show that nelfinavir inhibits lytic cell-free transmission of HAdV, indicated by the suppression of comet-shaped infection foci in cell culture. Comet-shaped foci occur upon convection-based transmission of cell-free viral particles from an infected cell to neighboring uninfected cells. HAdV lacking ADP was insensitive to nelfinavir but gave rise to comet-shaped foci, indicating that ADP enhances but is not required for cell lysis. This was supported by the notion that HAdV-B14 and -B14p1 lacking ADP were highly sensitive to nelfinavir, although HAdV-A31, -B3, -B7, -B11, -B16, -B21, -D8, -D30, and -D37 were less sensitive. Conspicuously, nelfinavir uncovered slow-growing round HAdV-C2 foci, independent of neutralizing antibodies in the medium, indicative of nonlytic cell-to-cell transmission. Our study demonstrates the repurposing potential of nelfinavir with postexposure efficacy against different HAdVs and describes an alternative nonlytic cell-to-cell transmission mode of HAdV.
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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 Socratic graph.