The study, published in Science Advances, presents GHP-88310 as a clinical candidate for infections caused by orthoparamyxoviruses, including human parainfluenzaviruses and measles virus. The research team used a large high-throughput screening campaign to identify and optimise an early lead and then characterised the candidate in multiple infection models.
GHP-88310 was tested in rodent and non-rodent animal models and in human airway organoid cultures. Key findings include broad antiviral activity with once-daily oral dosing, good tolerability at very high concentrations in both rodents and higher mammals, and evidence from animal studies of a high barrier to viral escape from inhibition.
- Primary clinical focus: human parainfluenzavirus type 3, a cause of severe pneumonia in high-risk adults.
- Secondary focus: measles, which has resurged with outbreaks in the US, Mexico and Canada.
- Discovery approach: high-throughput screening and lead optimisation, followed by in vivo and organoid testing.
The project involved the Center for Translational Antiviral Research at Georgia State, the Emory Institute for Drug Development, and the University of Washington Medical Center. Funding came from the National Institute of Allergy and Infectious Diseases of the National Institutes of Health. Lead authors emphasised that GHP-88310 is a promising inhibitor for this virus family and that the programme was designed to address the needs of patients affected by re-emerging orthoparamyxoviruses.
Difficult words
- orthoparamyxovirus — a family of related viruses that infect mammalsorthoparamyxoviruses
- candidate — a drug proposed for testing in patients
- high-throughput screening — a fast lab method to test many samples
- optimise — to improve a compound or process for best results
- organoid — a small lab-grown tissue that models an organ
- tolerability — ability to accept side effects without stopping
- inhibitor — a substance that slows or stops a biological process
Tip: hover, focus or tap highlighted words in the article to see quick definitions while you read or listen.
Discussion questions
- What advantages and limitations do you see in testing a drug in both animal models and human airway organoid cultures?
- How might a high barrier to viral escape affect the long-term usefulness of an antiviral drug? Give reasons based on the article.
- Why is it important to focus on diseases like human parainfluenzavirus type 3 and measles, according to the information in the article?
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