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Viruses are very small infectious agents consisting of nucleic acids (RNA or DNA) wrapped with the shield made of proteins or capsid. The virus lives solely as a parasite, it has no its own metabolism but it uses metabolism of the host for the synthesis and assembly of their active particles – virions.

The Life Cycle of The Virus

The life cycle of the virus is very simple. The virus enters the body and finds the suitable cells. Then it enters the cells by penetrating the cell membrane and releases its genetic material, DNA or RNA. The genetic material of the virus enters the nucleus of the host cell and uses host enzymes for the synthesis of cellular mRNA which controls the synthesis of new elements for the construction of new viruses through the ribosome. These protein components are expressed on the cell surface. Replicated viral genetic material gets out of the host cell nucleus and travels to the surface of the cell, where using already created protein elements thousands of new viruses are assembled.


The main difficulty in designing of antiviral drugs is the nature of virus itself, as an obligate intracellular parasite, which has the reproductive cycle completely related to infected cell functioning. One of the most important tasks is to get the selectivity in antiviral drugs action.

Antiviral Drugs

Antiviral drugs act mainly by blocking the synthesis of viral DNA or RNA by inhibition of certain enzymes, while others block some other important steps in the life cycle of the virus. It is important to stress that there are antivirotics only for a few viruses, for other viruses there are vaccines and immunoglobulins, while for some viruses there is simply no effective treatment.
According to research conducted at The University of Iowa, antiviral drugs prevent the replication and spread of influenza virus type A by binding to the proton channel through which the virus penetrates the healthy cells. These findings are published 4th February 2012 in the journal Nature.

The New Research on Antivirotics Mechanism of Action

Mei Hong and John D. Corbett, a professor of chemistry at the University of Iowa and the Ames Laboratory associate at the Department of Energy in the United States, said that these results clarify results of previous, often contradictory studies and should direct the development of new antiviral drugs, primarily for various types of influenza, including pandemic H1N1.

Two papers released in 2008 in the journal Nature offer two different conclusions about where the antiviral drug Amantadine binds to a flu virus and how to prevent infection of the healthy cells. The work based on the x-ray shows that the drug binds to the lumen of the proton channel, travels inside the channel and blocks it, thus inactivating the virus. Another work is based on the technology of nuclear magnetic resonance (NMR) and it concluded that the drug binds to the viral surface protein, near the proton channel, and the virus is inactivated indirectly by changing the structure of the proton channel.

Hong’s research indicates that Amantadine, when in pharmacologically relevant amount of one molecule per channel, connects to the inner surface of the proton channel. However, research has shown that the drug, at a high concentration in the membrane, binds also to a secondary active site located on the surface of the viral proteins near the channel. "Our research is based on nuclear magnetic resonance in solid and irrefutably shows that the drug binds to the lumen of the channel, while the secondary active site binds only when it is in excess," says Hong. "The previous research, which relied on NMR in liquid, was using as much as 200 times the amount of medication needed, which would explain their results on how the drug binds to the active site of surfactants. The solution to this confusion means that chemists can now focus on developing drugs that will target real active site of the channel. "

Here's how the influenza virus uses proton channel and how Amantadine blocks the channel: viral infection begins with viruses binding to healthy cells. Healthy cell surrounds the flu virus and draw it into the cell using the process called endocytosis. Once it is inside the cell, the virus uses the protein called M2 to open a channel to a healthy cell. Through this channel protons from the healthy cells enter the virus and increase its acidity. This in turn drives the release of viral genetic material into the healthy cell. The virus then takes over cell resources to reproduce and spread viral particles. When Amantadine binds to the cell and blocks the M2 proton channel, the process stops, and the virus is no longer able to infect the cell.


Hong and his team have developed powerful techniques to study the proton channel using NMR spectroscopy, the technology of medical imaging using magnetic resonance. These technique allows them a detailed insight into the position of antiviral drug within the proton channel, and the scientists have been using it successfully to analyze the structure of the protein active site and to determine very accurately the distance between the drug and the protein. Scientists have also discovered that Amantadine rotates while binding to the active site within the proton channel. That means it do not fill the channel. Hong says this opens up a lot of room for development of new drugs that could block the channel better, thus stopping the flu, and also avoiding the development of resistance to the drug.

Klaus Schmidt-Rohr, a chemistry professor at the University of Iowa and the Ames Laboratory chemist superior, Sarah Cady, PhD student and external associate of the chemistry department of the University of Iowa, William DeGrado, George W. Raiziss professor of biochemistry and biophysics and a professor of chemistry at the University of Pennsylvania; Cinque S. Soto, a doctoral student in the department of biochemistry and biophysics at the University Pennsylvania and Jun Wang, a graduate student in the Department of Chemistry at the University of Pennsylvania, are other contributors to this study. The study was financed through donations. National Science Foundation has donated 687 411 dollars, 616 $ 295 donated by the National Institutes of Health.