Anti-Viral Agents - Overview
Sections
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.
References:
Bhatia, Harmeet Kaur, Harmanjit Singh, Nipunjot Grewal, and Navreet Kaur Natt. "Sofosbuvir: A Novel Treatment Option for Chronic Hepatitis C Infection." Journal of Pharmacology & Pharmacotherapeutics 5, no. 4 (2014): 278–84. https://doi.org/10.4103/0976-500X.142464.
Connell, Bridgette J., and Hugues Lortat-Jacob. "Human Immunodeficiency Virus and Heparan Sulfate: From Attachment to Entry Inhibition." Frontiers in Immunology 4 (November 20, 2013). https://doi.org/10.3389/fimmu.2013.00385.
Dogra, Pranay, Emily B. Martin, Angela Williams, Raphael L. Richardson, James S. Foster, Nicole Hackenback, Stephen J. Kennel, Tim E. Sparer, and Jonathan S. Wall. "Novel Heparan Sulfate-Binding Peptides for Blocking Herpesvirus Entry." PLOS ONE 10, no. 5 (May 18, 2015): e0126239. https://doi.org/10.1371/journal.pone.0126239.
Dyer, A P, B W Banfield, D Martindale, D M Spannier, and F Tufaro. "Dextran Sulfate Can Act as an Artificial Receptor to Mediate a Type-Specific Herpes Simplex Virus Infection via Glycoprotein B." Journal of Virology 71, no. 1 (January 1997): 191–98.
"Ganciclovir and Valganciclovir: An Overview - UpToDate." Accessed June 18, 2018. https://www-uptodate-com.proxy.medlib.uits.iu.edu/contents/ganciclovir-and-valganciclovir-an-overview?search=ganciclovir&source=search_result&selectedTitle=2~105&usage_type=default&display_rank=5.
"HHV-6 & Encephalitis | HHV-6 Foundation | HHV-6 Disease Information for Patients, Clinicians, and Researchers | Apply for a Grant." Accessed June 20, 2018. https://hhv-6foundation.org/associated-conditions/hhv-6-and-encephalitis.
"Neuraminidase Inhibitors for Treatment of Influenza A and B Infections." Accessed June 18, 2018. https://www.cdc.gov/Mmwr/preview/mmwrhtml/rr4814a1.htm.
Images:
"Cytomegalovirus Retinitis." Wikipedia, June 16, 2018. https://en.wikipedia.org/w/index.php?title=Cytomegalovirus_retinitis&oldid=846108194.
"09G0036_lores.Jpg (700×482)." Accessed June 18, 2018. https://phil.cdc.gov/PHIL_Images/06011999/00016/09G0036_lores.jpg.