category_faq

FAQ: Antivirals

What is the difference between an Antiviral and a Vaccine?

A vaccine is usually given as a preventative measure, they are made up of a weakened or killed version of the microorganism you wish to vaccinate against. When the vaccine is administered the immune system can build a protective response to the agent without suffering the full effects of the infection. An antiviral is a drug that is used to treat a patient already suffering from a viral illness (although in certain situations, antivirals can be used to prevent infection if administered shortly after exposure to a virus and before symptoms appear.

What are the most commonly used antivirals?

Probably the best known, and first commercially successful antiviral drug was Acyclovir, an antiviral nucleoside analogue which is used to treat herpes simplex virus infections (including cold sores and genital herpes). Ribavarin is a broad range antiviral and is active against a large range of viruses including the influenza viruses, hepatitis C and in combination with other drugs against Rabies. Since the huge increase in HIV/AIDS research the number of antiviral compounds discovered has increased dramatically.

What is HAART?

HAART or Highly Active Anti-Retroviral Therapy is a combination therapy given to HIV/AIDS patients. It is made up of a combination of antiviral drugs that target different and specific parts of the HIV life-cycle (such as virus entry into host cells) and synergistic enhancers that enhance the activity of some or all of the antivirals. Due to the high mutation rate of the HIV virus it develops resistance to antiviral drugs very quickly, especially if any of the drugs are missed or not taken properly (i.e. at the correct intervals or with/without food etc.), this allows selection of drug resistant forms of the virus to proliferate. Also, because a number of the drugs used in combination will inhibit each other maintaining effective treatment (and an effective combination of drugs) can become very difficult.

What are Interferons?

Interferons (IFNs) are naturally occurring compounds (known as cytokines) that show antiviral activity by preventing multiplication of virus in host cells. They are produced by the immune system in response to viral infection. The 3 main IFNs are IFN-α, IFN-β and IFN-γ, and are split into 2 groups: IFN-α, IFN-β are classed as Type I IFNs and IFN-γ Type II. The type I IFNs use the same receptor site on most nucleated cells and binding to this receptor inhibits viral replication. IFN-γ is a cytokine of the adaptive immune response and is involved in the regulation and development of specific immunity and in activation of the cells of the immune system. When administered to patients by intramuscular or subcutaneous injection, IFNs have been shown to inhibit infection of a number of viruses including as adenoviruses, enteroviruses, parvovirus and hepatitis B and C.

What are the main targets for antiviral agents?

Antiviral agents are generally directed at inhibiting the virus at certain stages of it’s life cycle within the body. Viral attachment and entry antivirals block binding of the virus to host cells, one method this can be achieved by is targeting surface receptors on the host cell (such as the CCR5 protein on T-helper cells that HIV utilizes). Amantadine belongs to a group of antiviral agents that act by inhibiting the uncoating stage of the viral life cycle. DNA polymerase inhibitors come in two forms: Nucleoside inhibitors such as acyclovir are incorporated into DNA blocking the DNA polymerase. Non-nucleoside DNA polymerase inhibitors act by directly binding directly to the DNA polymerase. Protease inhibitors act on the viral assembly and release phase of the viral life cycle oseltamivir acts on neuraminidase, an enzyme that allows the virus to break out of the host cell.

Why are there more antibiotics against bacteria than antivirals?

Antiviral agents tend to be directed at a single virus strain (or in some cases even individual serotypes of a viral strain). Bacteria, however, relative to viruses are hugely more complex, and fall into distinct families that share common characteristics. For example, a class of antibiotics called Tetracyclines inhibit bacterial protein synthesis by binding to the subunit of the bacterial ribosome, these antibiotics can therefore be used to target a number of bacteria, and bacterial infections. Antivirals, by contrast tend to be much more specific, and therefore limited in there spectrum of use. This is due to the fact that viruses are a lot simpler – both structurally (i.e. less physical parts to target) and functionally (in their replication cycle) than bacteria. As part of their life cycle involves utilising cell host machinery to replicate and infect, it is intrinsically more difficult to target a viral life-cycle process.

Why am I not given antivirals for a common cold, or stomach upset?

As described above, antivirals tend to be a lot more specific than antibiotics that are more ‘broad-spectrum’ in their approach. There are over 200 viruses that cause the common cold, each one with slightly different characteristics. As colds are usually self limiting and fairly short-lived, the time it would take to sample, test and characterise a virus causing a cold, the symptoms themselves would already have subsided! Also, there have not been 200 different antiviral drugs developed for every known cold causing virus. The same is true for viruses that cause gastroenteritis. The viruses known to be responsible for this illness rarely infect or survive for longer than 24-48 hours inside the human body. Interestingly, for both of these infections, it is the bodies reaction to the virus that causes more problems than the virus itself. In reality viral illnesses are rarely treated (rather the symptoms are ‘managed’) unless there is an underlying problem to be considered. These include immunocompromised patients (such as chemotherapy or HIV/AIDS patients who have a compromised immune system) and those more at risk from certain viruses such as infants or the elderly.

Do viruses become resistant to antiviral drugs?

Yes. Viral resistance to antiviral agents is a big problem. RNA viruses such as HIV have no ‘proof-reading’ machinery in their replication cycle, and replicate very quickly, they therefore have the capacity to evolve resistance to many antiviral agents very quickly. Other factors such as the size of the viral population, replication rate and the fitness of genetic variants also have an effect on how quickly or effectively a virus can evolve resistance to an antiviral agent. DNA viruses, which use a different polymerase to replicate, do have proof reading abilities, so that mutation rates in these viruses (such as the herpesviridae) are much lower. This is one of the reasons that HSV can be treated with a single drug, whereas HIV needs to be constantly challenged with a combination of antiviral agents.

What role does virus latency play in antiviral therapy?

Latency is a term used to describe a virus that has entered a ‘dormant’ state within the host. In this state, there is no active infection, but the virus retains the ability to ‘reactivate’ at a later stage. In the case of Herpes Simplex virus for example, latency occurs within neuronal cells and it is the movement of the virus from these cells down into the lips that produces the characteristic cold sore ‘tingle’ that is felt just before a cold sore appears. During the latent state few, if any virus proteins are expressed, meaning that there is no immune response to them, and no target for antiviral therapy. The ability of a virus to remain latent for extended periods of time, even in the presence of antiviral therapy makes for the total eradication of a virus from the host almost impossible.

References

  1. Encyclopaedia of Virology. 3rd edition. 2008. Edited by: Mahy, B.W.J. & van Regenmortal, M.H.V.  
  2. Fields Virology. 5th edition. 2007 Edited by: Knipe, D.M. & Howley, P.M. Published by Lippencott Williams and Wilkins.  
  3. Fundamental Virology 4th edition. 2001. Edited by: Knipe, D.M. & Howley, P.M. Published by Lippencott Williams and Wilkins.