New drug works against diseases like measles and croup

Researchers have developed a new oral antiviral drug candidate for the treatment of diseases caused by orthoparamyxoviruses, such as measles and croup syndrome, according to a new study.

The study in the journal Science Advances identified clinical candidate GHP-88310 for urgently needed, improved orthoparamyxovirus disease management in rodent and non-rodent animal models of infection.

Orthoparamyxoviruses, such as human parainfluenzaviruses, measles virus, and emerging henipaviruses, pose a significant threat to human health.

“We developed GHP-88310 to treat orthoparamyxovirus infections,” says Carolin Lieber, a senior postdoctoral fellow in the Center for Translational Antiviral Research in the Institute for Biomedical Sciences at Georgia State University and lead author of the study.

“GHP-88310 is the most promising inhibitor of this virus family that we have encountered in years of research.”

For this study, the researchers focused initially on human parainfluenzavirus type 3 as the primary clinical indication for drug development. Older adults, immunocompromised individuals, and adult hematopoietic stem cell transplant recipients are at great risk of life-threatening parainfluenzavirus pneumonia, with an estimated 3 million cases a year in the US requiring treatment.

There are no vaccines or therapeutics available to manage the disease. A secondary indication of GHP-88310 is measles, which has resurged in recent months with major outbreaks in large regions of the US, Mexico, and Canada.

“Re-emerging orthoparamyxoviruses such as the parainfluenzaviruses and measles virus are a major threat to children and vulnerable groups such as the immunocompromised,” says Richard Plemper, director of the Center for Translational Antiviral Research and senior author of the study.

“We specifically designed this drug discovery program to address the medical needs of these patient groups.”

To identify GHP-88310, the research team launched a large high-throughput drug screening campaign, identified and optimized an early generation lead, and characterized GHP-88310 in different animal model and human airway organoid cultures.

Exciting features of GHP-88310 include that the compound is very effective against a broad spectrum of orthoparamyxovirus disease when taken once daily by mouth, is well tolerated at very high concentrations in rodents and higher mammals, and has a high barrier against viral escape from inhibition in animals.

“High potency and excellent tolerability ensure a very wide safety margin, which is essential for a drug candidate developed for the treatment of highly vulnerable patient groups and children,” Plemper says.

Additional authors of the study are from the Center for Translational Antiviral Research in the Institute for Biomedical Sciences at Georgia State, the Emory Institute for Drug Development at Emory University, and the University of Washington Medical Center.

Funding for the study came from the National Institute of Allergy and Infectious Diseases of the National Institutes of Health.

Source: Georgia State University

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