Shotgun Approach to Keeping Viruses Off

Contributed by Guest Blogger: J. Moon ’14

The amount of human resources to develop therapeutics on a single-pathogen basis is limited. A single-pathogen approach is made more impractical with the ever increasing number of viral pathogens. But there are alternatives to this approach: broad-spectrum antivirals that target various groups of viral pathogens. Recent studies have found that LJ001, a broad-spectrum small molecule antiviral , is effective against numerous lipid enveloped viruses including Influnza A, filoviruses, poxviruses, areanviruses, bunyaviruses, paramyxoviruses,flaviviruses, and HIV-1. Against nonenveloped viruses, however, LJ001 has no effect.
The LJ001 antiviral acts by attaching to the membranes of both the cell and virus and inhibits virus-cell fusion. The antiviral begins by injecting itself into the lipid bilayer of the cell. But it is only activated upon contact with the other antiviral on the virus. Once activated, the molecule damages the lipid membrane of the virus. This damage to the lipid membrane results in loss of fluidity/rigidity that is necessary to undergo fusion into the cell. Since viral membranes do not have the ability to repair themselves, the viral membrane is deactivated by the LJ001 antiviral. Therefore, LJ001 is effective against various enveloped virus groups including the previously mentioned.
One of the first experiments was to see the comparative effects of the antiviral on viruses. The experiment consisted of testing enveloped and nonenveloped cells. The conclusion reached after data collection was that the LJ001 antiviral has no effect on nonenveloped viruses. Experiments were also conducted to determine whether or not the LJ001 antiviral was acting on the virus or on the cell. This included the introduction of the antiviral to the cell culture before and after attachment of the virions to cells. Results showed high infection rates near 100% for the cell cultures introduced to the antiviral after the virus attachment whereas infection rates for the cell cultures pre-treated with the antiviral were near zero. Experiments were also conducted with the antiviral being applied to a wide variety of large-scale lipid enveloped viruses. These results showed that there are varying degrees of effectiveness across different viruses. The conclusions reached on these observations are that LJ001 affects only non-enveloped viruses on varying degrees of effectiveness and that the LJ001 deactivates virions and prohibits virus-cell fusion.
What impact does this have on these enveloped virus groups? Although the lipid membrane of a virus remains fairly static from generation to generation, is it likely or possible that these viruses will somehow develop mechanisms to counter the effect of the antiviral? What are some possibilities?