New Potent Antiviral Against SARS-CoV-2, RSV and Other Respiratory RNA Viruses

Center for Translational Antiviral Research Reports New Class of Drugs with Activity Against SARS-CoV-2

The COVID-19 pandemic and the resurgence of infections from other respiratory RNA viruses, such as childhood respiratory syncytial virus (RSV), have led to an urgent need for the development of orally available broad-spectrum antivirals.

In a study published online Dec. 2, 2021 in Science, researchers at Georgia State University’s Institute for Biomedical Sciences report a new candidate ribonucleoside analog, 4′-fluorouridine (4′-FlU), which is a potent antiviral drug. activity against SARS. -CoV-2, RSV and other respiratory RNA viruses in cell culture, human organoids and various animal models when administered once daily orally.

“Mechanistically, we show that 4′-FlU is in a different class from molnupiravir that is currently under regulatory approval,” said Dr. Richard Plemper, Distinguished University Professor, director of the Center for Translational Antiviral Research at Georgia State and senior author of the study. “4′-FlU does not act as a mutagen, but induces termination of the viral polymerase, thereby aborting replication of the viral genome. There is an urgent need to expand the therapeutic arsenal against SARS-CoV-2 and 4′-FlU has strong development promise as a companion drug.”

The study tested 4′-FlU against several SARS-CoV-2 variants of concern in ferrets, which have emerged as a leading model for drug testing, and against respiratory syncytial virus in mice. The researchers found that this drug potently blocked SARS-CoV-2 replication, including the gamma and delta variants in the ferret, and efficiently suppressed the RSV load in the lungs of mice.

“We are pleased that 4′-FlU is the only orally available antiviral candidate currently being developed against SARS-CoV-2 that is active when given once daily,” said Dr. Julien Sourimant, lead author of the study and a researcher in Dr. Plemper’s lab at the Institute of Biomedical Sciences, “which should be an important asset in ensuring ambulatory compliance.”

Reference: “4′-Fluorouridine is an oral antiviral agent that blocks respiratory syncytial virus and SARS-CoV-2 replication” by Julien Sourimant, Carolin M. Lieber, Megha Aggarwal, Robert M. Cox, Josef D. Wolf, Jeong- Joong Yoon, Mart Toots, Chengin Ye, Zachary Sticher, Alexander A. Kolykhalov, Luis Martinez-Sobrido, Gregory R. Bluemling, Michael G. Natchus, George R. Painter, and Richard K. Plemper, Dec. 2, 2021, Science.
DOI: 10.1126/science.abj5508

This 4′-FlU study was the result of a collaboration between the Georgia State University team with researchers from Emory University and the Texas Biomedical Research Institute. The study was funded by public health grants from the National Institutes of Health/National Institute of Allergy and Infectious Diseases at Georgia State University.

Co-authors of the study are J. Sourimant, CM Lieber, M. Aggarwal, RM Cox, JD Wolf, J.-J. Yeong, M. Toots and R.K. Plemper at Georgia State University; C. Ye and L. Martinez-Sobrido at the Texas Biomedical Research Institute; and Z. Sticher, AA Kolykhalov, GR Bluemling, MG Natchus, and GR Painter at Emory University.