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Progress towards a new Fu vaccine, thanks to Tiny Tweak



This year's unexpectedly aggressive flu season reminds everyone that although the flu vaccine can reduce the number of people who infect the virus, it's still not 100 percent effective , Researchers report that fine-tuning for a small molecule drug is promising for the future production of new antiviral therapies that could help patients regardless of the burden they are infected with.

The researchers present their work today at the 255th National Meeting. Exhibition of the American Chemical Society (ACS). ACS, the largest scientific society in the world, holds the meeting until Thursday. It contains more than 1

3,000 presentations on a variety of scientific topics.

"This was a bad flu season with a highly contagious, aggressive burden, and the vaccine does not seem to work well, making the population, especially the young and elderly, vulnerable to serious illness or even death from the common flu "says Seth Cohen, Ph.D.

Since the flu season 2017-2018 began in October The Centers for Disease Control and Prevention (CDC) have reported more than 65,735 positive tests for the virus in the US, resulting in hundreds of deaths. The CDC attributes such an active season to the presence of a specific strain of the virus, influenza A H3N2. Influenza vaccines are less effective against H3-type viruses as these pathogens mutate more frequently than other strains after vaccine production. Although the vaccine is very effective at preventing people from getting flu in most years, this H3 error challenges scientists to seek more reliable treatments.

In order to develop an antiviral drug for influenza, scientists had to find an area within their structure that would prove vulnerable. The influenza virus is a lipid-enveloped RNA virus with a negative sense, that is, the genetic information it uses for replication is contained in RNA strands held in a protein sheath coated with a layer of fat. Rather than relying on a host's direct DNA replication process, like some other viruses, influenza depends on its own enzyme called RNA-dependent RNA polymerase. Therefore, scientists have consistently focused their research efforts on developing a drug that influences this viral process.

Cohen, who is from the University of California, San Diego and co-founder of Forge Therapeutics, notes that the RNA polymerase complex remains constant across many different versions and mutations of the influenza virus. Therefore, any therapies that are aimed at are not affected by the problem facing the vaccine. namely the H3 error. The RNA polymerase itself is divided into three subunits. Cohen has focused on a metal centered domain in one of the subunits.

"One of the main targets was a specific RNA polymerase subunit that uses the virus," says Cohen. "It's a nucleic acid-processing protein needed for the life cycle of the virus to replicate and replicate, and it's dependent on manganese metal ions." The subunit is based on two manganese ions to initiate the replication of the genetic information. Scientists have argued that a drug that could bind to the manganese ions would inhibit the protein's ability to function so the virus could not reproduce and spread throughout the body. This could weaken or even stop the virus altogether, treating the flu.

Cohen spent the last two years finding out how manganese ions bind within the RNA polymerase subunit to develop a better drug that could serve as a key Replication of the virus works. "We modified our small molecule drug to bind both manganese ions simultaneously," he says. He then tested the molecule on the RNA polymerase protein. "The modification has dramatically improved the effectiveness of the compound over previous drugs we created," he says. The team hopes it will be just as effective over the next few months as it challenges the whole influenza virus with the molecule.

"This is a medical intervention that will slow the virus down if it is not completely stopped," Cohen says. "The drug could potentially eliminate the virus alone or slow down its reproduction sufficiently for the body to clear it up, and it's like an antibiotic for a viral infection."


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