Effective oral antiviral against respiratory syncytial virus (RSV)

According to researchers at the Center for Translational Antiviral Research at Georgia State University.

The results published in the journal scientific advances, identify AVG-388 as a lead drug candidate that potently blocks the activity of viral RNA polymerase, an enzyme responsible for viral genome replication. RSV is a leading cause of lower respiratory tract infections in infants and immunocompromised people, but there is no effective treatment. The virus caused an estimated 33.1 million cases worldwide in 2015, requiring 3.2 million hospitalizations and resulting in 59,800 deaths.

Finding effective drugs to fight RSV has not been easy. Through mutations, RSV has bypassed advanced classes of candidates that prevent the virus from entering a cell. To overcome this problem, recent drug development efforts have focused on the RSV viral RNA-dependent RNA polymerase complex due to the possibility of a larger window of opportunity to target the virus during replication and transcription of the viral genome.

“We have identified the AVG class of RSV RNA synthesis inhibitors,” said Dr. . “Through chemical optimization, we have developed the clinical candidate AVG-388, which is orally active against RSV in infectious animal models. »

In addition, researchers have demonstrated potent antiviral activity in cultures of human airway epithelial organoids.

“In this study, we mapped an exciting drug target in RSV RNA-dependent RNA polymerase and established the clinical potential of the AVG class of inhibitors against RSV disease,” said Dr. Julien Sourimant, first author of the study and postdoctoral researcher. Researchers at the Center for Translational Antiviral Research at the Georgia State Institute of Biomedical Sciences.

The research team studied the treatment’s effect on virus replication at different oral doses, which should prevent or cure the disease. They showed that the treatment reduced viral loads by several orders of magnitude in the different disease models.

“Our results provide the basis for the formal development of the AVG class and the structure-guided identification of co-drugs with overlapping target sites but different resistance profiles,” said Plemper.

Study co-authors include Julien Sourimant (first author), Carolin M. Lieber, Jeong-Joong Yoon, Mart Toots and Richard K. Plemper of the Center for Translational Antiviral Research at the State Institute for Biomedical Sciences of Georgia; Mugunthan Govindarajan, Venkata Udumula, and Michael G. Natchus of the Emory Institute for Drug Development at Emory University; Kaori Sakamoto of the University of Georgia College of Veterinary Medicine; Joseph Patti of Aviragen Therapeutics Inc. (now at JP Biotech Advisors Inc.); and John Vernachio of Aviragen Therapeutics Inc.

The study was funded by the National Institutes of Health.

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Materials provided by Georgia State University. Note: Content can be edited for style and length.

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