The discovery of an oral antiviral drug that targets a key component of the respiratory syncytialvirus (RSV) polymerase has been made. It inhibits the production of viral genetic materials, which could prove to be a powerful treatment option for RSV.
Science Advances has published these findings. AVG-388 is identified as the leading drug candidate. It effectively blocks the activity RNA polymerase (an enzyme responsible for replicating the viral genome). RSV is a major cause of lower respiratory infections among infants and immunocompromised people. Unfortunately, no effective therapy exists. Globally, RSV caused 33.1 million cases in 2015 and required 3.2million hospitalizations. This virus also led to 59.800 deaths.
It has been difficult to find effective drugs for RSV. RSV has been able to escape the advanced candidate classes of drugs that could prevent it entering a cell through mutations. Recent drug development efforts focused on RSV’s viral RNA-dependent RNA polmerase complex to overcome this problem. This is because there may be a wider window of opportunity to combat the virus during its viral genome replication and transcription.
“We have identified AVG class inhibitors of RSVRNA synthesis,” stated Dr. Richard K. Plemper. He is a senior author and Distinguished University Professor. He also directs the Center for Translational Antiviral Research within the Institute for Biomedical Sciences. “We have created the clinical candidate AVG-388 through chemical optimization. It is orally effective against RSV in animal models.”
Researchers also found antiviral activity for human airway epithelium in organoid cultures.
“In our study, we identified an exciting druggable target within the RSVRNA-dependentRNA-polymerase, and established the clinical potency of the AVG inhibitor Class against RSV disease,” stated Dr. Julien Sourimant (first author, postdoctoral fellow in Center for Translational Antiviral Research, Institute for Biomedical Sciences, Georgia State).
The researchers examined the impact of treatment on viral replication at different oral doses designed to prevent or cure disease. They found that treatment significantly reduced the virus load in various disease models.
Plemper stated that “our results laid the foundation for formalization of the AVG Class and the structure-guided discovery of companion drugs with overlapping targets but distinct resistance profiles.”