Antiviral Agents - Overview
Antiviral Agents
Virustatic
Antiviral drugs are only effective against actively replicating viruses, they cannot kill the latent viruses present in the body.
Virus life cycle:
- Adhesion
- Entry
- Uncoating
- Synthesis and Assembly
- Virion release
Antiviral Agents & Mechanisms
Disrupt the viral envelope or surface proteins; prevent viral transmission:
Lipids, detergents, acids, and other anti-viral molecules can disrupt the surfaces of some viruses.
For example, citric acids disrupt the surface proteins of rhinoviruses.
Prevent Attachment:
Antibodies can neutralize viral attachment proteins on most viruses.
Peptide analogues can block host attachment protein; ex: drugs that block the HIV co-receptor necessary for entry.
Peptides can bind heparan sulfate (and other similar sites) on host cells, blocking the attachment of HIV and Herpes Simplex Viruses.
Prevent Penetration & Uncoating:
Inhibition of viral fusion proteins; Enfuvirtide blocks HIV fusion.
Inhibition of envelope fusion; Docosanol blocks envelope fusion of HSV and other viruses
Neutralize vesicle pH which inhibits viral uncoating; amantadine and rimantadine use this mechanism against Influenza A
Prevent penetration; Tromantadine is a drug that prevents HSV penetration.
Block receptors to sprevent uncoating; arilidone, disoxaril, and pleconaril prevent picornaviruses
Inhibit RNA or DNA synthesis; Block viral replication:
Nucleoside analogs:
– Acyclovir is active against Herpesviruses and Varicella-zoster virus (VZV); Valayclovir is a prodrug of acyclovir.
– Penciclovir is used to treat Herpes simplex viruses (specifically, cold sores), Varicella-zoster virus, Epstein-Barr infections, and Cytomegalovirus (CMV) infections; Famciclovir is a prodrug of penciclovir.
– Azidothymidine (aka, AZT), Dideoxyinosine, Stavudine, and Lamivudine are used to treat HIV infections
Nucleotide analogs:
– Cidofovir is used to treat Cytomegalovirus infections, especially in patients with AIDS, as well as Polyomavirus, Papillomavirus, and Herpes Simplex Virus infections.
– Adefovir is used to treat Hepatitis B (HBV) infections
Non-nucleoside polymerase inhibitors:
– Foscarnet is used to treat infections caused by Herpes virus, HIV, and Cytomegalovirus retinitis in AIDS patients.
– Nevirapine, Delvaridine, and, Efavirenze are used to treat Herpes virus and HIV.
Block Assembly and Release:
Protease inhibitors: Saquinavir, ritonavir, and indinavir, which are active against HIV.
Neuraminidase inhibitors: Zanamivir, and oseltamivir, which are active against Influenza A and B.