L25. Pharma - Antivirals I

Drugs used to treat infections caused by Herpes Simplex Virus (HSV).

Herpes Simplex Virus, a DNA virus.

Anti-HSV drugs that are similar to natural nucleotides that halt viral DNA synthesis.

Require phosphorylation by viral and host kinases to become active to inhibit viral DNA polymerase.

Enzyme within a virus that is necessary for the first phosphorylation step activating nucleoside analogues.

Antiviral drugs that target viral processes without significantly harming host cells.

Drugs that target viral DNA replication, e.g., acyclovir, valacyclovir, etc.

Requires multiple phosphorylation steps by both viral and host enzymes to become active and inhibit viral DNA polymerase.

Foscarnet directly binds to the pyrophosphate site of viral DNA polymerase, preventing nucleic acid synthesis. It doesn't require phosphorylation for activation.

Foscarnet preferentially targets herpesvirus DNA polymerase over host cellular DNA polymerase, making it a more selective antiviral.

Mutations in the viral DNA polymerase can lead to resistance to foscarnet, as the drug can no longer bind efficiently.

Foscarnet is effective against CMV retinitis, including ganciclovir-resistant infections, other types of CMV infections, and acyclovir-resistant HSV and VZV infections.

Foscarnet can cause nephrotoxicity (kidney damage), electrolyte abnormalities (calcium, phosphate, magnesium, potassium), and CNS toxicity.

Influenza viruses are classified into types A, B, and C, with type A being the most common and pathogenic.

Influenza viruses bind to host cells through the Hemagglutinin (HA) protein, which attaches to sialic acid receptors.

The influenza virion enters the host cell via endocytosis, and the M2 proton channel facilitates uncoating of the virus.

Amantadine blocks the M2 proton channel of influenza A, preventing uncoating and interfering with viral assembly.

Oseltamivir inhibits neuraminidase activity, preventing the release of new influenza virus particles from infected cells.

Interferons (IFNs) are potent cytokines that inhibit viral replication by signaling cells to produce antiviral proteins that degrade viral mRNA and activate immune cells.

IFNs trigger the production of enzymes like methylase and ribonuclease, which degrade viral mRNA, thus hindering the translation of viral proteins.

Attaching large polyethylene glycol (PEG) molecules to interferon proteins slows absorption, decreases clearance, and prolongs serum concentrations, allowing for less frequent dosing.

Common side effects of interferons include GI irritation, flu-like symptoms, neutropenia, fatigue, hair loss, and thyroid dysfunction.

Simeprevir is an antiviral drug that inhibits the NS3/4A protease, an enzyme essential for the maturation of viral proteins.

The NS3/4A protease is crucial for viral replication, as it generates mature viral proteins necessary for the virus to multiply.

Simeprevir also suppresses the host antiviral immune system, potentially leading to complications.

Simeprevir can cause anemia, itching, and temporary increases in bilirubin levels.

Adefovir, an antiviral drug, can cause kidney damage (nephrotoxicity) and enlarged liver (hepatomegaly).

Common side effects of entecavir include headaches, dizziness, and fatigue.

Acyclovir needs to be activated by three phosphorylation steps. The first step is done by the viral thymidine kinase, followed by the host kinases.

Acyclovir selectively accumulates in infected cells because it's activated by viral enzymes, making it more effective against HSV and VZV than CMV.

Valacyclovir is a prodrug that converts to acyclovir in the body. While they are similar in effectiveness against HSV, valacyclovir is more effective in treating herpes zoster.

Famciclovir is a prodrug that converts to penciclovir, which targets HSV and VZV similar to acyclovir. Penciclovir is phosphorylated more efficiently by viral kinase, but it has lower affinity for viral DNA polymerase.

Ganciclovir is primarily activated by viral kinases during HSV and CMV infections. During CMV, the UL97 gene encodes a specific viral phosphotransferase for activation.

Amantadine is effective against influenza A but not influenza B.

Amantadine is used for preventing and treating influenza A infections.

Amantadine can cause CNS side effects, especially when combined with certain other drugs.

Neuraminidase is an enzyme that helps influenza viruses escape from infected cells.

Oseltamivir is effective against both influenza A and B, unlike amantadine.

Hepatitis viruses are classified as A, B, C, D, and E. B and C are the most common.

Hepatitis B virus (HBV) is a DNA virus with a double-stranded genome.

Hepatitis C virus (HCV) is an RNA virus with a single-stranded genome.

Nucleotide/nucleoside analogues need to be converted into active forms by phosphorylation.