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Antiviral drugs

Viruses are among the most common and widespread causes of infectious diseases. They cause such illnesses as influenza, herpes simplex type I (cold sores of the mouth) and type II (genital herpes), shingles, viral hepatitis, encephalitis, infectious mononucleosis, and the common cold. Viruses remain one of the least understood and most difficult of all infectious organisms to control; but this is changing as more is learned about their structure and replication. Viruses consist of nucleic acid, either DNA or RNA., and a protein coat. Because viruses do not have the enzymes that are needed to manufacture cellular components, they are obligate parasites, which means they must enter a cell for replication to occur.

The nucleic acid of the virus instructs the host cell to produce viral components, which leads to an infectious virus. In some cases, as in herpes infections, the virus nucleic acid may remain in the host cell without causing replication of the virus and damage to the host (viral latency). In other eases, the production of virus by the host cell may cause the death of the cell. A major problem in treating some viral diseases is that latent viruses can become activated, frequently when the host undergoes stress, thereby producing infectious virus and cellular effects.

Many factors account for the difficulty in developing antiviral chemotherapeutic agents. The structure of each virus differs, and specific therapy is often unsuccessful because of periodic changes in the antigenic proteins of the virus. The need for a host cell to support the multiplication of the virus makes treatment difficult because the chemotherapeutic agent must be able to inhibit the virus without seriously affecting the host’s cells.

The greatest success against virus infections has been by increasing immunity through vaccination (influenza, poliomyelitis, measles, mumps, and smallpox) with live attenuated (weakened) or killed viruses. Vaccination has resulted in the total elimination of smallpox. While vaccination has proved to be effective against the specific virus used for smallpox, influenza is caused by viruses that constantly change their antigenic protein, thereby requiring revaccination as the antigenic makeup of the virus changes. Some virus groups contain 50 or more different viruses.

Passive immunization with serum or globulin (antibodies) from immune persons has been used to prevent viral infections. Immune globulins, such as those used against hepatitis, often cause adverse effects, however, and they are effective only for prophylaxis and not for treatment.

An antiviral agent must act at one of five basic steps in the viral replication cycle in order to inhibit the virus. The steps are (1) attachment and penetration of the virus into the host cell; (2) uncoating of virus – e.g., removal of the protein surface and release of the viral DNA or RNA; (3) synthesis of new viral components by the host cell as directed by the virus DNA; (4) assembly of the components into new virus; and (5) release of the virus from the host cell.