New antiviral drug targets measles outbreaks

 

Dr. Richard Plemper, from the newly founded Institute for Biomedical Sciences (IBMS) at Georgia State University (GSU), and his colleagues at the Emory Institute for Drug Development (EIDD) have developed a drug, called ERDRP-0519, which blocks the replication of the pathogen.

 

As reported in a recent issue of the journal Science Translational Medicine, virus levels were significantly reduced when infected animals received the drug by mouth. The drug also prevented the animals from dying of the disease.

 

In collaboration with Dr. Veronika von Messling from the Paul-Ehrlich-Institute, the Georgia-based researchers tested the drug by turning to a virus very closely related to measles virus, the canine distemper virus, which causes a highly lethal infection in ferrets. All of the animals treated with ERDRP-0519 survived infection with the distemper virus, remained free of the disease and developed robust immunity against the virus.

 

Scientists from the three institutes collaborated on the development of the drug and tested it in animals infected with a virus closely related to one that causes the measles. Plemper is the uniting figure among the three groups, having worked with von Messling in his native Germany, and then at EIDD before helping inaugurate the IBMS at GSU in January 2014. The Paul-Ehrlich-Institute developed the canine distemper model for measles, and von Messling’s lab is one of the world’s experts on the paramykovirus family of respiratory inflections—mumps, respiratory syncytial virus (RSV) and measles among them. While RSV stays in the respiratory tract, others, like measles, immediately spread to the lymph nodes, reproduce and become systemic.

 

This drug, one that can be produced cost effectively, stockpiled and administered by mouth, could boost eradication efforts by rapidly suppressing the spread of the virus during local outbreaks.

 

“To encourage compliance for the intended use, the drug must be orally available,” notes Plemper, “for once or twice daily dosage, be stable, cost-effective to produce and demonstrate an outstanding safety profile.”

 

Despite major progress in controlling the measles worldwide, annual measles deaths have remained constant at around 150,000 since 2007, and there has been a resurgence of the virus in European countries where it had been considered controlled. The reasons for this are the highly infectious nature of the virus and insufficient vaccine coverage, which in the developed world is mostly due to parents opting not to vaccinate their children.

 

“ERDRP-0519 is a small-molecule therapeutic,” Plemper points out. “It attenuates the virus and keeps titers low while the immune response still ‘sees’ the virus. Surviving animals have a very robust ongoing immune response. Take a case in preschool, for example. In two to three weeks after exposure in the same ‘air space,’ there is an 80-percent chance of catching the disease. The goal is to prevent infection and reduce the chance of transmitting the virus to others as well.”

 

“We are delighted to see our longstanding collaboration with Dr. Plemper and his team at the GSU IBMS come to fruition, and we look forward to continuing to leverage the medicinal chemistry and drug development capabilities at the EIDD in this and future collaborations with his group,” said Dr. Michael Natchus, director of operations at the EIDD, in an official statement.

 

Plemper said the drug could be used to treat friends, family and other social contacts of a person infected with measles virus, who have not developed symptoms yet but are at risk of having caught the disease.

 

“The emergence of strong antiviral immunity in treated animals is particularly encouraging, since it suggests that the drug may not only save an infected individual from disease but contribute to closing measles immunity gaps in a population,” Plemper said.

 

The researchers emphasize the drug is not intended as a substitute for vaccination, but as an additional weapon in a concerted effort to eliminate measles.

 

As experienced with many antiviral drugs, the virus can become resistant against this inhibitor. The investigators have examined the issue of viral escape and found that resistant viruses were in most cases less virulent. Equally important, the researchers observed that transmission of the resistant viruses between animals was impaired compared to the parent strain. These results are promising because they indicate resistance is unlikely to rapidly become widespread in the virus population.

 

While the drug is very encouraging thus far, additional research is needed before it can be considered for use in humans. “Next on our list,” says Plemper, “is tox testing to develop a full toxicology profile in animals.”