ArticleScience translational medicine2023
Efficacy of a brain-penetrant antiviral in lethal Venezuelan and eastern equine encephalitis mouse models.
Article in Science translational medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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.
The trial behind it
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
7 citing papers in PubMed, 8 citations in OpenAlex.
- Restructuring Antiviral Quinazolinone Frameworks to Derive and Optimize Inhibitors of Chikungunya Virus.ACS medicinal chemistry letters · 2025Article
- V4020 Venezuelan Equine Encephalitis Vaccine: Mitigating Neuroinvasion and Reversion Through Rational Design.Viruses · 2025Article
- Broad spectrum antiviral BDGR-164 provides protection against lethal neurotropic alphavirus infection in mice.Antiviral research · 2025Article
- The antiviral BDGR-49 provides protection from lethal, neurotropic Venezuelan equine encephalitis virus intranasal infection in mice.Journal of virology · 2025Article
- Syrian Hamsters Model Does Not Reflect Human-like Disease after Aerosol Exposure to Encephalitic Alphaviruses.Methods and protocols · 2024Article
- Neurological manifestations of encephalitic alphaviruses, traumatic brain injuries, and organophosphorus nerve agent exposure.Frontiers in neuroscience · 2024Review
- Mannich-Type Condensation and Domino Quinazolinone-Amidine Rearrangement Affords Ring-Fused Mackinazolinones with Anti-Amoebic Activity.Advanced synthesis & catalysis · 2023Article
Corrections and comments
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Authors and funding
27 authors at 5 institutions in 1 country.
Funding
Abstract
Venezuelan and eastern equine encephalitis viruses (VEEV and EEEV, respectively) are mosquito-borne, neuroinvasive human pathogens for which no FDA-approved therapeutic exists. Besides the biothreat posed by these viruses when aerosolized, arthropod transmission presents serious health risks to humans, as demonstrated by the 2019 outbreak of EEE disease in the United States that resulted in 38 confirmed cases, 19 deaths, and neurological effects in survivors. Here, we describe the discovery of a 2-pyrrolidinoquinazolinone scaffold, efficiently synthesized in two to five steps, whose structural optimization resulted in profound antiviral activity. The lead quinazolinone, BDGR-49, potently reduced cellular VEEV and EEEV titers by >7 log at 1 μM and exhibited suitable intravenous and oral pharmacokinetic profiles in BALB/c mice to achieve excellent brain exposure. Outstanding in vivo efficacy was observed in several lethal, subcutaneous infection mouse models using an 8-day dosing regimen. Prophylactically administered BDGR-49 at 25 mg kg
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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.