Researchers Hunt for Antiviral That Will Protect Against Multiple Influenza Strains

Researchers who are a part of the Drug Discovery team at the Southern Research Institute are dedicating their efforts to finding a new drug that will assist in the fight against an incredibly contagious respiratory infection that infects a whopping 3 million individuals annually: influenza.

The team’s approach? They are targeting a specific protein complex within influenza viruses called polymerase, which is a key player in viral replication.

Mohammad F. Saeed, PhD, a research scientist who is part of Southern Research’s Drug Discovery team, is leading the effort to develop effective treatment against the flu. According to the Centers for Disease Control and Prevention (CDC), vaccination is the best way to prevent infection, however, Dr. Saeed laments in a recent press release, “Influenza remains a big killer.”

According to the CDC, the flu accounts for 3,000 to 5,000 deaths in the United States alone, and the World Health Organization reports that it also accounts for 250,000 to 500,000 worldwide.

Each year, researchers work to determine which strains of the virus will be circulating in different parts of the world for that flu season, and develop vaccines against these particular strains. For example, in an interview with Contagion, Stephen Redd, MD (RADM, USPHS), director of the Office of Public Health Preparedness and Response (OPHPR), at the CDC, said, “Every year there is a decision process to decide what strains of influenza viruses go into the vaccine. For the Northern hemisphere, this takes place in the January-February timeframe.”

According to the press release, influenza A (H3N2) has accounted for the majority of flu-related infections this flu season (2016-2017). Despite the fact that this year’s vaccine imparts a degree of protection against this strain of influenza, the press release indicates that CDC officials warn that it really only reduces risk of influenza infection by one third. For this reason, Dr. Saeed and his team are on a dedicated mission to develop a “broad-spectrum antiviral that’s effective against several strains of the virus,” an antiviral that he hopes will offer individuals increased protection against a number of strains that may not be included in the seasonal flu vaccine.

Dr. Saaed explained, “Let’s say we have a pandemic like we had in 2009 with swine flu—the vaccine wouldn’t work against that because that is a different variety of influenza. Every now and then, you see a different strain of influenza entering [the] human population and becoming more prevalent globally because the existing vaccines are ineffective against the new strain. To generate a vaccine for the new variety, it would take six to nine months, or a year.”

According to the CDC, the swine flu, H1N1, was first detected back in April of 2009, and this strain of the virus “was a unique combination of influenza virus genes never previously identified in either animals or people.” It was responsible for 284,000 deaths worldwide. A broad-spectrum antiviral may work to prevent another pandemic such as this.

In addition to the threat of swine flu, there is an additional threat posed by avian influenza (H5N1). Although it is uncommon for this type of flu to infect humans, there is a high mortality rate associated with cases where human transmission has occurred. Furthermore, no vaccines are available that can offer protection against these particular strains.

Dr. Saeed explained, “Normally, these viruses don’t jump species, from birds to humans, but our biggest concern is, what if they acquire mutations in nature so that they can more frequently infect humans? That would become a big problem, because these viruses are more pathogenic than the influenza virus we see in human populations.”

Despite the fact that researchers have developed vaccines to assist in the fight against influenza, these viruses are ever-changing and they have the potential to develop resistance to medications typically prescribed to treat them. In fact, adamantanes, a class of influenza antiviral drugs consisting of amantadine and rimantadine, are actually no longer recommended by the CDC for use in the United States for this reason. Even more unsettling, oseltamivir, one of the most commonly used antivirals, has also shown “sporadic resistance.” According to the CDC, resistance to oseltamivir “is currently low, but this can change.”

Just the idea of this being a possibility has Dr. Saeed and his team are working on treatments that target polymerase, a protein complex that is “relatively consistent across several influenza virus subtypes.”

Dr. Saeed explained, “Without these proteins, the virus cannot replicate. If we can inhibit those proteins, we can stop the virus in its tracks.” Furthermore, since polymerase appears to play such a significant role in viral replication, it will be rare for mutations to occur in the protein complex. Therefore, there is a lower chance that that the influenza strains will be able to develop resistance to a “polymerase-targeted drug.”

With a “compound collect” containing around 500,000 samples that can be used for “screening against influenza viruses,” the Southern Research team is well-equipped to tackle their goal. In fact, 200,000 compounds have already been tested and thus far, they’ve already had around 900 “hits, or agents that showed activity against influenza.” The next step is additional screening so that the researchers can see if these agents are actually working against their intended target.

Dr. Saeed concluded, “Influenza pandemics have killed millions of people, and in the case of an outbreak of a highly pathogenic influenza virus, there just won’t be time to develop a vaccine. We need a drug against this threat.”

Dr. Saaed and his team are not the only researchers who are on a hunt for a treatment that will effectively reduce the incidence of both seasonal and pandemic virus strains. A research team from the University of Chicago, Princeton University, and Imperial College in London are also making strides when it comes to the development of “universal” vaccines, or vaccines that are designed to target “more conserved components of the influenza virus.”