Medicine That Treats Gout Could Also Battle COVID-19

AHA Publisher — Mon, 13 Sep 2021 07:00:43 +0000

University of Georgia via Newswise – As COVID-19 cases continue to skyrocket across the U.S. and the world, few options are available for treating patients infected with the SARS-CoV-2. But new research from the University of Georgia offers hope for a viable therapeutic to combat the disease that has claimed more than 4 million lives worldwide. Published in Nature’s Scientific Reports, the study found that probenecid has broad antiviral properties, making it a prime candidate to combat not only SARS-CoV-2 infection but also other common and deadly respiratory viruses like RSV and flu. Probenecid is an FDA-approved medication that’s primarily used to treat gout, and it’s already widely available in the U.S. The drug has been on the market for over 40 years and has minimal side effects. “There’s really nothing out there to safely fight these viruses,” said Ralph Tripp, lead author of the study and GRA Eminent Scholar of Vaccine and Therapeutic Studies in UGA’s College of Veterinary Medicine. “This antiviral works for all RNA respiratory viruses we tested, including SARS-CoV-2. RSV, coronavirus and flu all circulate in the same season. Bottom line is you can potentially reduce infection and disease using this one oral drug.” Blocking Viral Reproduction Viruses work by coopting a person’s own cells to replicate and produce more of the virus. Probenecid blocks that replication process, keeping the virus from infecting the individual’s cells. In clinical development at the pharmaceutical company TrippBio, Tripp showed the drug works as a prophylactic prior to virus exposure and as a post-exposure treatment in animal models against SARS-CoV-2 and flu. The drug also has proven effective in fighting the RSV in vitro, and in vivo studies are in progress. Although the drug would primarily be used after a person is positive for the virus, the prophylactic findings mean people with known exposures could also potentially take the drug to prevent getting sick. COVID-19 Treatment Options Limited The current go-to treatments for seriously ill COVID-19 patients, remdesivir and monoclonal antibodies, can only be given through an IV. And by the time a COVID patient needs them, it’s often too late. “These treatments have seen some effectiveness against SARS-CoV-2, but they’re very expensive and very hard to come by,” Tripp said. “In reality, there are only a handful of options that can actually be used because of the cost, restricted IV usage, and lack of access. That’s not very useful to the world.” Probenecid, on the other hand, is widely available. Primary care physicians could prescribe a pill to patients, and they could pick it up at their local drugstore. Repurposing drugs that are already approved to work against one problem is common. For example, remdesivir was originally intended to fight Ebola virus… In addition to preventing illness before it starts, probenecid may also potentially increase the efficacy of other treatments. Probenecid is already used to up the potency of some antibiotics, so it’s possible the medication could work in conjunction with other COVID-19 treatments as well. Now the researchers are investigating what dosage of probenecid could have the biggest impact fighting viruses in people. TrippBio is set to begin clinical trials of the medication within the year. “SARS-CoV-2, RSV and flu have a huge impact on health systems throughout the world,” Tripp said. “Probenecid has a potent antiviral effect against these viruses, and it works safely.” This article has been modified. To read the original article click here.

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Landmark Discovery May Lead to Safe, Effective Antiviral Drugs Against COVID-19

AHA Publisher — Fri, 09 Apr 2021 07:00:03 +0000

Argonne National Laboratory via News-Medical – The COVID-19 vaccines currently rolling out are providing hope that the spread of the disease can be halted. But infection rates are still high, and for those who contract COVID-19, the search for effective treatments remains important. Researchers examining the atomic structure of SARS-CoV-2, the virus that causes COVID-19, have made a landmark discovery that could contribute critical information to the design of safe and effective antiviral drugs in the fight against the virus. “Understanding enzymes goes hand in hand with understanding their atomic structures -; and the higher resolution the better, because subtle differences can affect the interpretation. We wanted the best data possible, so we went to the APS.” (Natalie Strynadka, University of British Columbia) Using a powerful X-ray beam to study SARS-CoV-2 proteins in crystallized form, a team from the University of British Columbia (UBC) has observed -; for the first time ever -; the virus’s main protease, an important enzyme of the virus, performing its function. This widely pursued antiviral target is a central enzyme that allows the virus to cut up large proteins called polyproteins into smaller functional units, a process necessary for the virus to be replicated and infect other human cells. “What we’ve captured at high resolution is one of the important steps in that process that has never been visualized before in any viral protease of this class,” said Natalie Strynadka, the UBC biochemistry professor who led the research team with colleague Mark Paetzel. The research was published in Nature. The breakthrough was made possible by the Advanced Photon Source (APS), a U.S. Department of Energy (DOE) Office of Science User Facility at DOE’s Argonne National Laboratory. The APS produces X-rays that are roughly a billion times brighter than those used by doctors and dentists, allowing researchers to examine the structure of the coronavirus protease in very fine detail at the atomic level. Data was captured at the General Medical Sciences and Cancer Institutes Structural Biology Facility at beamline 23-ID-B at the APS. The newly uncovered information may be of particular interest to scientists worldwide who are racing to develop antiviral treatments for COVID-19. If the main protease is inhibited by a small molecule drug, the polyproteins won’t be clipped into functional pieces, effectively blocking viral replication and subsequent transmission. “We now have a much better blueprint of these mechanistic structures that will inform making the best inhibitor possible,” Strynadka said. ”Better knowing the structure as we now do helps guide drug research, narrowing the field of potential targets instead of having to screen billions of potential molecules.” Michael Becker, a protein crystallographer with Argonne’s X-ray Science Division, said Strynadka’s research stands out because the team was focused on understanding the mechanism of the protease. “This understanding will improve everyone else’s work in designing drugs,” Becker said. ”Because the more deeply you understand how something works, the better the chance you have of controlling or stopping it.” Remote access capabilities at Argonne made it possible for the researchers in British Columbia to collect data in real time and to manipulate the APS beamline located about 2,200 miles away in Illinois. UBC team members Jaeyong Lee and Liam Worrall shipped crystals of the SARS-CoV-2 main protease preserved in liquid nitrogen from Canada to Argonne. Workers at the APS were on hand to answer questions, ensure the working order of the equipment, and load the samples. “The remote interface is fantastic. It’s almost like being there,” Strynadka said. ”We’re very thankful for the use of the APS. Canada does have a national synchrotron facility, but it currently doesn’t have the same capability as the APS, which is a very high-level facility with micro-focused beams. Understanding enzymes goes hand in hand with understanding their atomic structures -; and the higher resolution the better, because subtle differences can affect the interpretation. We wanted the best data possible, so we went to the APS.” To read the original article click here.

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Medicine That Treats Gout Could Also Battle COVID-19

Landmark Discovery May Lead to Safe, Effective Antiviral Drugs Against COVID-19