Ever read about the discovery of a new protein in a virus coating, and think, “I know that must matter to someone, but who?” It matters to the people who make antivirals. Each newly discovered protein could allow them to take control of viruses like puppeteers. Here’s how anti-virals work, and why they’re amazing.
Some science headlines are undeniably cool. They announce new psychological understandings, new dinosaurs, new landmarks in space exploration. And then there are the other kind of headlines – ones that seem almost to challenge us with how uninteresting they are. There’s always a headline about proteins in any group of dull headlines. A particular protein has been found in the coating of a certain virus. A specific enzyme has been found to help synthesize RNA in one kind of cell. Another protein can manipulate one sequence of DNA in one specific way.
The headlines are dull, to the lay reader, because they apply only to very specific organisms and they do extremely limited things. But for people who work to develop antivirals, that’s exactly what’s exciting about them.
DNA, RNA, and proteins, are the three indispensable molecules of life. If you can manipulate the right protein, in just the right way, you can do anything to any creature.
And that’s the principle of antivirals. Researchers target a protein inside a virus — a protein that is specific only to that virus (or that group of viruses), and sabotage that protein. By picking their targets carefully, they can make a virus self-destruct spectacularly, without harming the proteins in any of the human cells around the virus.
Antiviral drugs seldom kill viruses outright. They are more effective when they disable proteins that allow viruses to replicate. Since viruses need their host cell to replicate, a way to nip the process in the bud is never allowing the virus to successfully penetrate the host cell. Some scientists see this as a possibility for highly-effective HIV medication. An antiviral drug would potentially lock onto the same receptor proteins that the virus would attach itself to, giving the virus no way to bind to the outside of a cell.
But that’s letting a virus off too easy, and if you’re a master virus puppeteer, you don’t want to do that. Once a virus is inside a cell, it needs to disrobe, taking off its coating, so it can get to work replicating itself. One of the earliest antivirals, rimantadine, took advantage of this need. Developed by Du Pont all the way back in 1963, rimantadine takes out the protein that starts the uncoating sequence in a flu virus. So a virus can get into a cell, but it can’t do a damn thing once it’s in there.
If scientists can’t find the right protein to keep a virus from entering the cell and uncoating while it’s in there, they can also sabotage the process by which the virus copies itself. You’ve heard of nucleotides, the building blocks of DNA. Nucleosides are the building blocks of nucleotides. One trick that designers of antivirals can use is synthesizing things that look very much like useful nucelosides or nucleotides. Once the virus starts making use of these analogs, they break down the enzymes that build DNA and RNA in the first place. The virus’s own standard operating procedure is used to produce the stuff that destroys its production.
This strategy is what produced the first really successful antiviral. In the 1970s, antivirals were recognized as a possible treatment option for viral infections, but few thought that really effective antivirals could be specific enough to kill off viruses without killing off human cells in the virus’s vicinity. George Hitchings and Gertrude Elion came up with acyclovir, an antiviral that shut down the herpes virus and nothing else. Their success – success that included a Nobel Prize for both of them – caused other scientists to really start taking an interest in what antivirals could do.
Once a virus has penetrated a cell and replicated, it needs to get out again, moving through the body to infect new cells and make more offspring. This is where another kind of antiviral comes into play. To get out of the cell, the virus breaks out an enzyme called neuraminidase, which lets it move through the cell wall. No enzyme, no escape. A group of flu antivirals destroy the enzyme. The flu can replicate inside cells that it has already infected, but can’t ever move on to infect new cells.
Antivirals are examples of how far science can come with incremental strides. Hard-working researchers have been doing valuable research, finding out that one enzyme does this, and one glycoprotein does that, and finding ways to exploit their discovery. Each small discovery, while not making exciting headlines, has made for an exciting change in the way we treat, and hope to treat, viruses that threaten thousands, and sometimes millions, of people’s lives.
And, if we listen to researchers, there are still leaps to be made in this area. One particular antiviral drug may affect not one virus, but any human cell infected with a virus. Any infected cell dies off, taking its occupants with it, and clearing the infection from the body. The drug’s creators hope to use it to shut down not a viral infection, but all viral infections. It could be a form of penicillin for viruses. And how does it work?
By targeting one particular protein, of course.