According to researchers at Georgia State University's Center for Translational Antiviral Research, an oral antiviral medication that targets a crucial component of the respiratory syncytial virus (RSV) polymerase and prevents the synthesis of viral genetic material has been identified.
The discovery may lead to the development of a potent remedy for RSV disease.
The research, which was published in the journal Science Advances, identifies AVG-388 as the top therapeutic candidate that successfully inhibits the viral RNA polymerase, which is in charge of replicating the viral DNA. However, there is no effective treatment for RSV, which is a major cause of lower respiratory infections in newborns and immunocompromised people.
In 2015, the virus is thought to have been the cause of 33.1 million cases worldwide, 3.2 million hospital admissions, and 59,800 fatalities.
It has been difficult to find RSV medications that work. RSV has managed to evade advanced candidate classes, which stop the virus from entering a cell, by modifications. The viral RNA-dependent RNA polymerase complex of RSV has been the focus of recent drug development attempts to address this problem due to the potential for a wider window of opportunity to combat the virus during viral genome replication and transcription.
“We have identified the AVG class of inhibitors of RSV RNA synthesis,” said Dr. Richard K. Plemper, senior author of the study, Distinguished University Professor and director of the Center for Translational Antiviral Research in the Institute for Biomedical Sciences at Georgia State. “Through chemical optimization, we have developed the clinical candidate AVG-388, which is orally efficacious against RSV in animal models of infection.”
“In this study, we have mapped an exciting druggable target in the RSV RNA-dependent RNA-polymerase and established the clinical potential of the AVG inhibitor class against RSV disease,” said Dr. Julien Sourimant, first author of the study and a postdoctoral fellow in the Center for Translational Antiviral Research in the Institute for Biomedical Sciences at Georgia State.
In addition, the researchers showed strong antiviral activity in organoid cultures of human airway epithelium.
The study team looked into how different oral doses of medication used to treat or prevent disease affected viral replication. In the various illness models, they showed that therapy significantly decreased viral burden.
According to Plumper, the findings establish the groundwork for the formal formation of the AVG class and the structure-guided discovery of companion medicines with similar target locations but different resistance characteristics.