You may have heard that viruses are not even considered to be alive, but they sure can cause a lot of damage when they infect us! Learn how antiviral drugs can selectively inhibit viruses even though they use our own cellular machinery to reproduce.
Viruses Hijack Our Cells
When you’ve got the flu and you’re lying at home in bed, totally lethargic, achy and miserable, it might only add to your discomfort to realize that your cells are under attack from hijackers. That’s right; viruses are teeny, tiny hijackers that can only reproduce by getting into your cells and mooching off of the machinery your body has worked so hard to produce.Adding insult to injury, it’s really hard to treat viruses with drugs.
This is because so many of the processes necessary for viral reproduction are the same processes our own cells need to carry out their day-to-day lives. Usually, we just have to let a viral infection run its course. The idea is eventually our immune system will get rid of the virus and leave us with some immunity against future infections.But for some viruses, treatment is really necessary. In this lesson, we’ll learn about three major classes of antiviral drugs that are used to treat viral infections such as the flu, herpes and hepatitis.
Inhibiting DNA/RNA Synthesis
The first major class of antivirals we’ll talk about is the nucleoside analogs. You may remember that when you add phosphate groups to nucleosides, you get nucleotides, which are the building blocks of the nucleic acids DNA and RNA. The general strategy of these drugs is to be decoys that trick the enzymes involved in DNA and RNA synthesis. If the enzymes add a decoy nucleotide into the growing DNA or RNA chain, the chain will stop growing.
Thus, nucleoside analogs block viral reproduction by inhibiting DNA and RNA synthesis.The drug acyclovir and its derivatives work in this way. It’s a pro-drug, meaning that initially it is a harmless molecule, but it can get transformed into an active drug.
Conveniently, this transformation happens specifically in infected cells, because certain herpes viruses have an enzyme called thymidine kinase, which kicks off the change of acyclovir into an active drug. The viruses end up shooting themselves in the foot, so to speak. Acyclovir is often used to treat infections with herpes simplex viruses, which cause cold sores and genital herpes. It can also be used to treat the herpes viruses that cause chicken pox and shingles.Another important nucleoside analog is ribavirin. In addition to blocking viral DNA and RNA synthesis, ribavirin increases the mutation rate of RNA viruses until there are so many errors in the viral genetic sequence that the virus is destroyed.
You can compare this to making so many typos while writing an e-mail that the person you send it to can’t even tell what you were trying to say. Ribavirin is commonly used to treat the hepatitis C virus, which causes liver disease.
Inhibiting Viral Entry/Exit
The next class of antiviral drugs we’re going to cover is drugs that inhibit viruses from getting into and out of host cells. Clearly, this is a very important step in viral reproduction, since, like I said before, viruses must be inside host cells in order to replicate themselves. But, then they have to get out of the host cell in order to move on and infect new cells and new hosts.A common cold sore remedy, docosanol, which is the active ingredient in the drug Abreva, inhibits the entry of the herpes virus into host cells.
It does this by preventing the viral envelope from fusing with the host cell’s plasma membrane. If the host cell’s doors are locked, the virus can’t get in and do what it wants to do most, which is make lots of copies of itself.Two drugs that are used to treat influenza, the virus that causes the flu, are zanamivir and oseltamivir.
These drugs go by the commercial names Relenza and Tamiflu. Usually, when you get the flu, you just let it run its course and spend a few days at home in bed until you feel better. However, influenza can sometimes cause really severe symptoms and even death, and these drugs are used in those cases. Both zanamivir and oseltamivir inhibit the viral enzyme neuraminidase. Neuraminidase allows the influenza virus to get out of the host cell after its replication, so these drugs inhibit viral exit. It’s like keeping the newly-formed viruses locked up in jail so that they can’t go on to cause further damage.
Inhibiting Viral Spread
One last type of antiviral treatment is interferon.
You may have heard of interferons before. There are several different types, and they are a part of our immune system’s natural defense against viruses. They don’t inhibit viruses directly, but you could say that they ‘interfere’ with viral spread. One type, the interferon alpha, inhibits the spread of viruses by alerting our cells that there’s a virus around and directing them to produce various types of antiviral proteins that can block viral reproduction in many ways.
Interferon alpha, in addition to being made naturally in our bodies, is commonly given to patients that have viral hepatitis infections, which cause liver disease. Alternatively, instead of giving the patients the interferons themselves, you can give a drug called imiquimod, which stimulates the body’s own production of interferons. Imiquimod can be used to treat genital warts that are caused by human papillomaviruses.
Today we’ve learned about a few different kinds of drugs that can effectively treat viruses. This is no small accomplishment, since viruses are little hijackers that use our own cells’ machinery to replicate. This means that it’s hard to find drugs that can inhibit viruses without inhibiting our own cells.We learned that nucleoside analogs are decoy molecules that block viral DNA and RNA synthesis. Two examples of these drugs are acyclovir and ribavirin, which are used to treat herpes viruses and hepatitis C. When the drug is inserted into a growing DNA or RNA chain instead of a real nucleotide, the chain stops growing and viral reproduction is inhibited.
In addition, ribavirin increases the mutation rate of RNA viruses, causing so many typos that the virus is destroyed.Next, we heard about drugs that prevent viruses from getting into and out of host cells. Docosanol is a drug that is used to treat cold sores. It prevents the herpes simplex virus envelope from fusing with the host cell plasma membrane and thus prevents the virus from entering the host cell. And zanamivir and oseltamivir are two drugs that inhibit the influenza enzyme neuraminidase.
Neuraminidase allows the influenza virus to exit host cells after it replicates, so these drugs prevent viral exit. The idea is that they keep the virus locked up in jail where it can’t do any more damage.Finally, we learned that our own bodies produce interferon alpha to alert our cells of viral infections and induce them to make antiviral proteins.
These interferons can also be given to patients, for example in the case of hepatitis C infection. Alternatively, the drug imiquimod is often used to stimulate interferon production and can help treat genital warts.
After you’ve completed this lesson, you’ll have the ability to:
- Explain why it’s difficult to treat viruses using drugs
- List drugs from the three antiviral classes discussed and tell what they’re used to treat