Oral Antiviral Advances for Future Pandemic Preparedness

Obeldesivir (GS-5245) is an experimental small molecule oral antiviral that shows promise as a new weapon in the arsenal against future pandemics. Several researchers from the University of North Carolina at Chapel Hill’s Gillings School of Global Public Health have co-authored a recent study, published online in the journal Science Translational Medicine on May 22, detailing the findings of this innovative drug.

The research emerges from a collaboration between biopharmaceutical company Gilead Sciences and the Sheahan and Baric Labs at the Gillings School, the same partnership that previously researched remdesivir (marketed as Veklury®). Remdesivir gained emergency use authorization in 2020 during the COVID-19 pandemic and was later fully approved. It functions by inhibiting the SARS-CoV-2 virus's ability to replicate, thereby shortening recovery time and reducing disease severity and mortality. However, remdesivir's intravenous (IV) administration necessitates healthcare visits, posing a limitation during widespread outbreaks.

Since the onset of the COVID-19 pandemic, scientists have been developing an oral antiviral drug derived from remdesivir’s parent nucleoside to facilitate easier administration. "Oral bioavailability means that you can take the medicine by mouth and do not need to visit a health care setting to receive treatment," explains Timothy Sheahan, PhD, a virologist and assistant professor of epidemiology at the Gillings School. “This is a potential limitation for remdesivir, which is an IV drug. With a prescription, you could take an oral antiviral at home just like you would take Tylenol.”

In the recent study, oral obeldesivir demonstrated a significant reduction in disease severity in mice infected with various coronaviruses, including SARS-CoV-2, SARS-CoV, and MERS-CoV. Researchers noted a dose-dependent decline in viral replication, weight loss, lung injury, and loss of lung function. Additionally, when combined with nirmatrelvir, an active ingredient in Paxlovid, obeldesivir further improved outcomes in COVID-19-infected mice.

These promising results advocate for the continued development of obeldesivir as a potential broad-spectrum anticoronaviral medication. Gilead Sciences has completed a Phase 3 clinical trial involving over 2,000 individuals who tested positive for COVID-19 but lacked risk factors for severe disease and were not hospitalized.

"While obeldesivir did not achieve its primary clinical goal of reducing symptom duration in a standard risk population in the Phase 3 OAKTREE trial, it remains a promising drug with no identified safety concerns," Sheahan notes. He attributes the challenging assessment to the current state of immunity and reduced disease severity compared to the early pandemic days. Initially, the drastic differences between placebo and treated groups were more evident due to higher hospitalization and mortality rates. The current study aimed at measuring the reduction in symptom duration in individuals not at high risk for severe COVID-19, making the subtle differences harder to detect amidst milder disease.

Ultimately, the clinical trial confirmed obeldesivir’s safety in a diverse population. Like remdesivir, obeldesivir may continue to be tested for efficacy in humans and could be quickly deployed against emerging coronaviruses. The research team also remains optimistic about the potential of this broad-spectrum antiviral medicine against other RNA viruses.

How to obtain the latest research advancements in the field of biopharmaceuticals?

In the Synapse database, you can keep abreast of the latest research and development advances in drugs, targets, indications, organizations, etc., anywhere and anytime, on a daily or weekly basis. Click on the image below to embark on a brand new journey of drug discovery!