Weapons and Hope

In a recent article entitled “How to cure diseases before they have even evolved,” New Scientist reports on the promising results of several research teams to develop a new class of antiviral drugs that would each target a whole range of viruses, including strains of viruses that have not even emerged yet.  The new approach: host-targeted antiviral therapy.

The Problem of Viral Mutation

H1N1 Influenza Virus

One of the truly frightening features of viruses is their tendency to mutate into new strains, which can often yield new properties of transmissibility and virulence.  This is a prime consideration that has led to the incredible hype surrounding the new H1N1 influenza strain.  The scientific community has expressed fears that H1N1, which currently seems no more serious than a seasonal flu strain, may be in the process of mutating into a serious pandemic virus.  Public health officials have made analogies to the 1918 Spanish flu, which is believed to have followed this course of mutation over the summer (though there is some debate surrounding this claim, which can be seen here).

As is described in another post today, there are also fears that rogue, terrorist, or careless scientists could engineer new strains of viruses.  New Scientist quotes Michael Goldblatt of Functional Genetics as he explains the problem of emerging viruses:

If you look at the viruses that are the biggest threats of modern times, most of them were unknown through human history: HIV, SARS, Ebola. You don’t know where the next one is coming from. How do you develop therapeutics for the unknown and unknowable, given that you won’t have time to develop a vaccine for a new agent after it appears?

Goldblatt’s question is rhetorical, as his research team at Functional Genetics as well as a few other groups now may have an answer.

A New Approach

New Scientist explains the conventional approach to antiviral drugs:

The conventional strategy for developing antivirals is “one bug, one drug” – finding a drug that blocks viral replication by binding to part of a viral protein. The trouble is, any minor mutation that slightly changes the shape of the protein can render these drugs useless, as is happening with Tamiflu. The hundreds of millions of dollars governments worldwide have spent stockpiling this drug could well turn out to be futile.

TSG101, one of the proteins targeted by Goldblatt's team

In contrast, Goldblatt’s team is not targeting viral proteins.  Instead, they are targeting host (human) proteins.  Even at the most basic levels, molecular biology courses teach students that viruses hijack host cells not only through synthesis of their own viral proteins but also by co-opting host proteins.  Goldblatt’s team has developed new drugs that prevent viral replication by inhibiting specific host proteins needed by viruses to break out of host cells.  The results have been incredibly promising, with the drugs showing effectiveness against a wide range of viruses in a cell culture.  Moreover, targeting of host proteins should not pose a threat to normal cellular function (and thus human health); in fact, Goldblatt’s team has “identified more than 100 different human proteins that flu viruses need to replicate but which cells can survive without.”

Other research teams have shown positive results using similar approaches.  Under Vishwanath Lingappa, Prosetta Bioconformatics is developing drugs that target host proteins involved in the assembly of the viral protein coating, which is necessary for viruses to co-opt new cells.  Philip Thorpe of the University of Texas Southwestern Medical Center in Dallas is taking a slightly different approach, targeting a different host molecule.  With the help of Peregrine Pharmaceuticals, his team is developing a drug that will target a fatty substance that is normally only found on the inner surface of a cell membrane, but is found on the outer membrane when the cell is virally infected.  The drug is an antibody that binds to the exposed fatty substance, triggering the immune system’s destruction of the target cell.

Promises for the Future

It is still early for these host-targeted antiviral drugs, as only human trials will truly reveal if targeting host proteins and other host molecules results in serious side effects.  However, if the approach works, New Scientist explains that it would be “a medical breakthrough on a par with the discovery of penicillin.”  By targeting host molecules rather than viral proteins, these drugs would not only be able to immediately treat for new viruses but also mitigate the problem of viral mutations.

Read the article for a comprehensive look.