General anti-viral drug

October 18, 2005 1:08 AM

Is there ever any chance of a generic anti-viral drug being developed?

Currently, anti-viral innoculations are very specific - a specific one for every year's flu, for instance, generally based on dead or modified versions of the virus itself to spark recognition in your immune systems.

However viruses generally operate in the same way (with a few distinctions like retroviruses) - are there, or will there every be a drug that will kill all viruses in general based on the common structure and way viruses operate? Leading on to this - are there any good viruses that you wouldn't want to kill?

posted by Jimbob to health & fitness (7 comments total)

Is there ever any chance of a generic anti-viral drug being developed?

Interferon?
posted by Rothko at 1:19 AM on October 18, 2005

Aaah interferon...good point. Although the side effects seem pretty nasty: "rarely, patients experience their hair falling out, dizziness and depression" - it's not something they'd ever give you to cure the common cold, really. It's really just a boost for your natural immune defense.
posted by Jimbob at 1:31 AM on October 18, 2005

viruses generally operate in the same way

I would not agree with that statement.
posted by grouse at 1:56 AM on October 18, 2005

All viruses are parasites. There are various classes of viruses, each with different molecular and genetic "designs".

There are no "good" natural parasites, by definition, although good is a bit of a value judgement and a few biologists have suggested that viruses contribute to a vibrant, diverse gene pool resilient to environmental shocks, and so their presence provides an evolutionary benefit to all organisms in a larger sense.

As an aside, biologists do sometimes use artificial viruses to transform organisms with new genetic material. We can take advantage of the infective properties of viruses to inject what we want into something. This is how gene therapy works for humans. In theory, this would be a good thing, although in practice patients have died (one at my place of employment).

Drug therapies are generally aimed at one component or another of a natural virus. One drug type might be aimed at the genes or proteins that replicate the virus' genetic information. Another might be aimed at the genes or proteins that build the viral protein coat.

AIDS drugs, for example, fall in the category of anti-retroviral drugs, since HIV is a retrovirus.

One class of anti-retroviral drugs includes protease inhibitors. PIs work by interfering with a protein called a "protease", an enzyme that cleaves or cuts other proteins. HIV uses proteases to cut up proteins to make new HIV virus coats. By inhibiting proteases, HIV can't replicate.

Another class is called a reverse-transcriptase inhibitor, e.g. AZT, which interferes with a protein called reverse transcriptase (RT). RT is a protein that makes copies of viral RNA. Block RT and HIV can't copy its own genome. No genome, no virus to infect other cells.

There are other classes of anti-retroviral drugs that target specific components of the virus, ultimately aiming to keep the retrovirus from replicating.

Other drugs work on other viruses similarly, by trying to interfere with the genetic or protein machinery of viruses. For example, RNA interference (RNAi) is a therapy being developed to deal with various other viral diseases, such as Epstein-Barr.

RNA interference can "knock out" or "silence" viral mRNAs, which make the proteins needed to make new copies of viruses. This interferes with the lytic cycle of viral replication.

Interferons work a little differently, by indirectly working on viruses through manipulating the machinery of your immune system, ramping up some components while winding down others.

There is no one drug that works as a magic bullet, mainly because the components that different classes of viruses use are biochemically different. These biochemical differences make it necessary to customize the approach taken to handle the virus.

Additionally, viruses mutate at different speeds. Natural selection leaves behind surviving viruses that don't respond to your drug the same way the second time around. So you have to constantly adjust what you're taking.

This is a major reason why AIDS patients eventually die: the virus mutates to the point where the drug cocktail no longer has any effect. You adjust the cocktail and hope for the best, or you die.

Another reason that drugs don't work well is that drugs can interfere with the natural machinery of your own cells, in addition to interfering with viral machinery. A good metaphor is giving chemotherapy to cancer patients — you hope to kill the bad stuff without killing off too much good stuff.

Sometimes the cure is worse than the disease, your immune system collapses, and you die of a secondary infection.
posted by Rothko at 2:57 AM on October 18, 2005

Of course there will never be a drug universally applicable for all, or even most, viruses. But components of the innate immune system (of which the interferons are examples) can kill a pretty broad range of viruses, and it should be possible in the future to use them in new ways to treat or prevent viral infections. A recently discovered cellular protein called ZAP, for example, can kill both retroviruses and alphaviruses (which are both single-stranded RNA viruses, but completely unrelated). APOBEC proteins are effective against retroviruses as well as hepatitis B virus (a double-stranded DNA virus). Then there are the Toll-like receptors which are a family of cellular proteins that recognize particular motifs common among viral molecules, such as double-stranded RNA, and initiate an immune response.

The problem is that each virus has its own little evolutionary niche, and doesn't like being killed by its host, so it does its best to evolve around these defenses in whatever way it can.

However viruses generally operate in the same way

Grouse has the right idea. Just because retroviruses make DNA from an RNA template doesn't mean they're the only bizarre, crafty, ingenious MFs on the block. Not at all. Saying viruses are uniform betrays a lack of appreciation of evolution. Even among retroviruses there is so much variety and so much that we don't even understand yet. The state of virology now will look pretty primitive in 100 years, if the world is still around then.

are there any good viruses that you wouldn't want to kill?

I can't think of any beneficial virus, so probably no. But you wouldn't want to utterly destroy them if you could, because they've been extremely useful in biology and will hopefully be useful therapeutically (eg, in gene therapy).

Lastly, RNA interference can be as effective against nonlytic viruses (eg retroviruses) as against lytic ones.
posted by shoos at 4:38 AM on October 18, 2005

are there any good viruses that you wouldn't want to kill?

Interesting question - there's debate as to what came first, viruses or transposons (ie., whether or not viruses were bits of our DNA that escaped).

Viruses use the parts of the host's cell machinery to replicate itself, so a drug that would inhibit viral replication in a broad manner would likely affect the host, which is undesireable.

Immune therapy seems to be the way to go when managing viral infections. Natural Killer (NK) cells are good at getting rid of infected cells. Alpha-gal-ceramide has shown some promise in "super activating" NK cells so they are better at killing virally infected cells. Also, there's some promise in stimulating the (innate-ish) immune system with Toll-like Receptor (TLR) ligands. There's a molecule that stimulates cells through TLR7 (which normally recognizes microbial RNA) that has been quite successful in treating genital herpes.
posted by PurplePorpoise at 11:49 AM on October 18, 2005

Viruses can be 'good' depending on what organism you are. Some viruses infect bacteria and supply virulence factors that can potentially increase the bacteria's fitness in certain environments (like inside a human).
posted by NucleophilicAttack at 6:07 PM on October 20, 2005