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Getting the bugs out of the flu
ATLANTA—The Emory Institute for Drug Discovery and Zirus Inc., a biotechnology company based in Buford, Ga., have inked a collaboration agreement and research understanding to develop novel compounds to treat infectious viral disease. One of the goals of the partnership is to develop a broad-spectrum antiviral, much the same as the broad-spectrum antibiotics that currently exist to treat bacterial infections.
Zirus uses a proprietary method for identifying genes and gene products in host cells that, when blocked, can prevent viruses from multiplying. Over the past several years, either alone or in collaboration with partners, including the Centers for Disease Control and Prevention (CDC), Zirus has identified, licensed and filed patents on more than 1,000 such targets.
Zirus has also identified a number of drugs currently approved for indications other than infectious disease that appear to also be effective in blocking targets that Zirus has identified. These drugs, having already successfully obtained a nod from the FDA, have the potential to reach the market quickly to address significant unmet medical needs for infectious diseases.
The Emory team working with Zirus has successfully brought a number of important drugs to market and is generally regarded as one of the top chemistry groups in the world.
Since viruses invade human cells and hijack proteins to reproduce, the goal of the combined forces of the two partners is to shut down the pathway for the virus to reproduce.
"We seek a way to shut down the gene product, the proteins, so that virus can't replicate," explains David Perryman, president and CEO of Zirus. "We find and validate those host proteins, while Emory will then develop drugs to hit the key molecule in this equation."
"Over the years, viruses have shown that they can outsmart vaccines and antiviral drugs such as protease inhibitors by mutating and developing resistance," says Dr. William O 'Brien, Zirus' chief medical officer. "As a result, there is no effective vaccine for HIV, each year we need a new vaccine for the seasonal flu, the effectiveness of vaccines for variations of swine flu and avian flu remain questionable, and the cocktail of drugs taken by AIDS patients is constantly changing. In our labs, or in collaboration with the CDC, we have successfully blocked, among other viruses, Ebola, Marburg, HIV, influenza, RSV, rhinovirus, herpes virus, dengue fever virus, cowpox virus, measles virus, BVDV and others."
Perryman adds, "the collaboration with Emory is designed as a true partnership between Zirus and a world-class group of chemists with a track record of designing successful drugs. Zirus is a relatively small company that's really good at targeting viruses, while Emory is a large entity that is really good at drug discovery. It's extremely helpful to a company like ours to have a university partner."
Zirus has experienced some national notoriety in the recent past due in part to an animation on its Web site, www.zirus.net, that illustrates how a virus invades a cell. That expertise was used widely in the media during 2009's H1N1 outbreak.
The Emory team is led by Dr. Dennis Liotta, the Samuel Candler Dobbs Professor of Chemistry and head of the Emory Institute for Drug Discovery. Liotta has won numerous awards for his work, has served as a consultant to a number of major pharmaceutical companies and is the inventor of record for several clinically important antiviral drugs. Liotta is also a member of Zirus' Scientific Advisory Board.
"While I have successfully worked for many years developing antiviral drugs, the Zirus approach to blocking host cell genes and gene products represents a new paradigm in dealing with infectious disease that may address some of the shortcomings of conventional programs," Liotta says. "Infectious disease needs a multi-pronged attack, and the Zirus host targets appear to represent the 'third leg of the stool' along with vaccines and traditional antivirals that attack the virus."
In the past, Liotta explains, approaching the treatment of the host proteins involved undesirable side effects. It is now known that the body can find other pathways to accomplish the work of a targeted cell that might be compromised or destroyed. In addition to the most well-known indications, such as fighting tough bugs such as the seasonal and H1N1 flu, HIV and others, the new approach could one day be successfully used in fighting bioterrorism.
"A broad-spectrum antiviral would help in the fight against bioterroism in the sense that when an attack takes place, time is lost in determining what the pathogen exactly is," Liotta says. "If we know something that many viruses have in common, we can more effective treat the patient."
Under the agreement, Zirus will be responsible for delivering targets for certain agreed upon diseases, screening potential drugs in its viral assays and conducting certain animal trials. The Emory Institute for Drug Discovery will construct chemical libraries and optimize drug candidates.
"Zirus will identify the host factor, and Emory will identify a modulator of that factor, in essence to prevent that virus from doing whatever it does in the body," explains Liotta.
Currently, according to Liotta, the six-month-old partnership involves three post-doctoral chemistry students, who are conducting computational analyses. When "hits" are identified, additional human resources will begin to work on addition development.
Both sides would share in the financial return on the results. Neither partner would share details of that part of the agreement.
Zirus is a private biotechnology company with a proprietary platform of more than 1,000 human host targets essential for viral replication and is developing repurposed drugs and preclinical small-molecule antagonists. Its platform addresses all major antiviral markets, including pandemic/seasonal flu, HIV, HCV, RSV, common cold viruses, bioterror threats and broad-spectrum antiviral drugs.
The Emory Institute for Drug Discovery was established in August 2009 at Emory University in Atlanta, with the dual mission of carrying out early-stage discovery and preclinical drug research aimed at developing small-molecule therapeutics and training new generations of researchers in a multidisciplinary drug discovery environment.