The respiratory syncytial virus (RSV) is perhaps one of the most feared by parents in winter, since it mainly affects young children and is one of the main causes of lower respiratory tract infections in infants and immunocompromised individuals, for which there is no there is an efficient therapeutic treatment. The virus caused an estimated 33.1 million cases worldwide in 2015 that required 3.2 million hospitalizations and resulted in 59,800 deaths.
That is why the discovery of a group of scientists from the Center for Translational Antiviral Research at Georgia State University, who found a drug oral antiviral that targets a key part of the virus polymerase and inhibits the synthesis of viral genetic material, a finding that could provide an effective treatment against RSV disease.
The findings, published in Magazine Science Advances, identify AVG-388 as the main drug candidate, which effectively blocks the activity of viral RNA polymerase, an enzyme responsible for viral genome replication.
“We have identified the AVG class of RSV RNA synthesis inhibitors,” said study lead author Richard K. Plemper, MD, Distinguished University Professor and Director of the Center for Translational Antiviral Research at the State Institute of Biomedical Sciences. from Georgia. “Through chemical optimization, we have developed the clinical candidate AVG-388, which is orally effective against RSV in animal models of infection.”
In addition, the researchers demonstrated potent antiviral activity in organoid cultures of human airway epithelium.
“In this study, we have mapped an exciting drug target to 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 fellow at the Center for Translational Antiviral Research at the Georgia State Institute of Biomedical Sciences.
The research team investigated the effect of treatment on viral replication at different oral doses intended to prevent or cure the disease. They showed that the treatment reduced the virus load by several orders of magnitude in the different disease models.
“Our results lay the groundwork for the formal development of the AVG class and structure-guided identification of complementary drugs with overlapping target sites but distinct resistance profiles,” said Plemper.