Antiviral Drugs
Antiviral drugs are a class of medication used specifically for treating viral infections. Like antibiotics, specific antivirals are used for specific viruses. Antiviral drugs are one class of antimicrobials, a larger group which also includes antibiotics, anti-fungal and anti-parasitic drugs. They are relatively harmless to the host, and therefore can be used to treat infections.
They should be distinguished from viricides, which actively deactivate virus particles outside the body. They are medications for the treatment of infection by retroviruses, primarily HIV. Different classes of antiretroviral drugs act at different stages of the HIV life cycle. Combination of several (typically three or four) antiretroviral drugs is known as Highly Active Anti-Retroviral Therapy (HAART).
Antiretroviral drugs are broadly classified by the phase of the retrovirus life-cyle that the drug inhibits. There are thus five broad classifications of antiretroviral drugs in development, though only the first three classes currently have licensed examples:
- Reverse transcriptase inhibitors (RTIs) target construction of viral DNA by inhibiting activity of reverse transcriptase. There are two subtypes of RTIs with different mechanisms of action: nucleoside-analogue RTIs are incorporated into the viral DNA leading to chain termination, while non-nucleoside-analogue RTIs distort the binding potential of the reverse transcriptase enzyme.
- Protease inhibitors (PIs) target viral assembly by inhibiting the activity of protease, an enzyme used by HIV to cleave nascent proteins for final assembly of new virons.
- Fusion inhibitors block HIV from fusing with a cell’s membrane to enter and infect it. There is currently only one FDA-approved drug in this class, enfuvirtide, marketed as Fuzeon.
- Integrase inhibitors inhibit the enzyme integrase, which is responsible for integration of viral DNA into the DNA of the infected cell. There are several integrase inhibitors currently under clinical trial but none are commercially available.
- Entry inhibitors block HIV-1 from the host cell by binding CCR5, a molecule on the host membrane termed a co-receptor that HIV-1 normally uses for entry into the cell together with a primary receptor.
The general idea behind modern antiviral drug design is to identify viral proteins, or parts of proteins, that can be disabled. These “targets” should generally be as unlike any proteins or parts of proteins in humans as possible, to reduce the likelihood of side effects. The targets should also be common across many strains of a virus, or even among different species of virus in the same family, so a single drug will have broad effectiveness. For example, a researcher might target a critical enzyme synthesized by the virus, but not the patient, that is common across strains, and see what can be done to interfere with its operation.
The number of useful antiviral compounds is rapidly expanding. The current antiviral agents FactFile is a convenient key to the vital statistics of antiviral compounds to be used as an aide m?moire when reading or writing antiviral literature. A miniportrait is provided for each of the antiviral compounds. The minimum criteria for inclusion of new compounds in the FactFile is the granting of an investigational new drug application with the realistic potential for medical or veterinary application. Several compounds that were subsequently withdrawn from further development are also included because of their historical importance or particular interest. The compounds are listed alphabetically according to their generic names together with systematic chemical names, common names and chemical structures. The compounds are grouped by virus targets; thus, the list is sub-divided into inhibitors of DNA viruses, RNA viruses, and retroviruses.