0731 GMT June 16, 2019
The goal of some anti-viral therapies, therefore, is to buy more and give the immune system a leg up on the virus. A new study led by Bruce Freedman and Ronald Harty in the Department of Pathobiology of the University of Pennsylvania School of Veterinary Medicine demonstrates a way to do that, by reducing the ability of the virus to exit a host cell and spread. Their work showed that blocking a calcium-signaling pathway could inhibit not only the Ebola virus, but also Marburg, Lassa and Junin viruses, all sources of deadly infections, EurekAlert reported.
The work paves the way toward designing a potential broad-spectrum drug that could serve as a therapy for a number of serious viral infections.
"Our work is aimed at handicapping the virus so that the immune system has time to respond," said Freedman.
"We could also imagine this type of drug would be part of a cocktail therapy, like those used for HIV, to cripple the virus at different stages of its life cycle," echoed Harty.
Because viruses must hijack host cell proteins to complete their life cycle and reproduce, the Penn Vet scientists have focused on developing drugs that interfere with the host proteins and mechanisms that viruses depend on.
They conducted initial experiments using non-infectious viral-like particles, or VLPs, the production of which is orchestrated by the virus' matrix protein and which bud from cells in a similar manner to the infectious virus. This allows for the observation of host-virus interactions without using dangerous live viruses.
Calcium signaling is a key regulator of many cell processes, and earlier studies by these authors had suggested that calcium was needed by these and other viruses. The researchers followed up by examining how cellular calcium levels responded when VLPs were being produced in cells. They found that virus matrix proteins triggered significant upticks in calcium levels, which were prevented when the researchers introduced a mutated version of a gene that encodes a calcium channel called ORAI1 into the host cells.