Center for Translational Antiviral Research Reports Novel Drug Class with Activity Against SARS-CoV-2
The COVID-19 pandemic and resurgence of infections by other respiratory 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.
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Interesting. Broad Spectrum Anti Viral Drugs.Shotgun approach.
How about getting to a sharpshooter approach to address Covid -19 pandemic?
Covid -19 infects by fusing with Receptor CELLs in the Human Ecosystem. Since it infects practically every organ in the body, the wide-spread Ace-2 Receptor Cell is the prime suspect as the receptor cell.
Three strategies possible.
1. Do not allow the Lifeless Virus which has entered to fuse with the Ace-2 Cell, by using Protease Inhabitors , to assist the Human Immune system in its battle. If the Virus cannot fuse it will be flushed out from the well hydated persons body?
HIV drugs use this strategy (Protease Inhabitors?) for HIV Positive cases against the Retrovirus which causes Human Immuno Deficiciency Syndrome?
2. if Person is infected , minimise infection, by focusing on viral load, and not allowing the Covid-19 Virus to increase and multiply with various enzymes and blockers as well as physics based mechanicaldevices. These can slow down and make it difficult for further fusion
with receptor cells, till Human Body defense mechanisms can kick in an flush out the invading hordes.
3. Mutations fn the Virus is a given. Every mutation will change the structural shape of the Vius Polymer, and can either enhance its ability to fuse with the Receptor Cells in the Human Body or reduce its ability to do so. To move from Pandemic to Endemic , strategies to reduce its (Spike Protein which is the front – end) ability to fuse with the Human ecosystem Receptor CElls,, should be encouraged. Mother Nature on her own, seems to have Carried out 32 mutations to create the Omicron Variant, which appears to be a milder but faster spreading
Covid-19 virus of the Original version from Wuhan. Asper reports this Omicron Variant can infect even vaccinated people. though most cases of Omicron cases are reportely unvaccinated cases.
4. The importance of Structural Biology and Biochemistry of fusion of the Receptor Cells needs to be better understood, to determine if a future doomsday variant can emerge, before the Human Race is protected vide its expertimental vaccines currently in use. Computational Biochemistry of such polymeric protien structures would have been useul. From 32 data points ( Mutations of the spike protin , we can safely predict the next likely mutation based on predictive analytics) and whether such a mutation can be deadly or on the right path towards endemic.
Views ezpressed are personal and not binding on anyone.