Center for Translational Antiviral Research Reports Novel Drug Class with Activity Against SARS-CoV-2Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the official name of the virus strain that causes coronavirus disease (COVID-19). Previous to this name being adopted, it was commonly referred to as the 2019 novel coronavirus (2019-nCoV), the Wuhan coronavirus, or the Wuhan virus.”>SARS-CoV-2
The COVID-19First identified in 2019 in Wuhan, China, Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It has spread globally, resulting in the 2019–20 coronavirus pandemic.”>COVID-19 pandemic and resurgence of infections by other respiratory RNARibonucleic acid (RNA) is a polymeric molecule similar to DNA that is essential in various biological roles in coding, decoding, regulation and expression of genes. Both are nucleic acids, but unlike DNA, RNA is single-stranded. An RNA strand has a backbone made of alternating sugar (ribose) and phosphate groups. Attached to each sugar is one of four bases—adenine (A), uracil (U), cytosine (C), or guanine (G). Different types of RNA exist in the cell: messenger RNA (mRNA), ribosomal RNA (rRNA), and transfer RNA (tRNA).”>RNA viruses such as respiratory syncytial virus (RSV) in children has caused an urgent need for the development of orally available broad-spectrum antiviral therapeutics.
In a study published online on December 2, 2021, in Science, researchers in the Institute for Biomedical Sciences at Georgia State University report a new candidate ribonucleoside analog, 4’-fluorouridine (4’-FlU), that has potent antiviral activity against SARS-CoV-2, RSV and other respiratory RNA viruses in cell culture, human organoids and different animal models when administered orally once daily.
“Mechanistically, we show that 4’-FlU is in a different class from molnupiravir that is currently considered for 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, 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 developmental promise as a companion drug.”
In the study, 4’-FlU was tested against different 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 RSV burden in mouse lungs.
“We are excited that 4’-FlU is the only orally available antiviral candidate currently developed against SARS-CoV-2 that is active when given once daily,” said Dr. Julien Sourimant, first author of the study and a researcher in Dr. Plemper’s lab in the Institute for Biomedical Sciences, “which should be a major asset in ensuring outpatient compliance.”
Reference: “4′-Fluorouridine is an oral antiviral 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, 2 December 2021, Science.
This research on 4’-FlU emerged from a collaboration of the team at Georgia State University with researchers at Emory University and the Texas Biomedical Research Institute. The study was funded by public health service grants from the National Institutes of Health/National Institute of Allergy and Infectious Diseases to Georgia State University.
Co-authors of the study include J. Sourimant, C.M. Lieber, M. Aggarwal, R.M. Cox, J.D. Wolf, J.-J. Yeong, M. Toots and R.K. Plemper at Georgia State University; C. Ye and L. Martinez-Sobrido at Texas Biomedical Research Institute; and Z. Sticher, A.A. Kolykhalov, G.R. Bluemling, M.G. Natchus and G.R. Painter at Emory University.