Anti-Viral Drugs (Notes) PDF

Anti-influenza virus Influenza virus types: A, B, C A is the most common and most pathogenic Virus through its Hemagglutinin attaches to host ce...

Anti-influenza virus Influenza virus types: A, B, C A is the most common and most pathogenic Virus through its Hemagglutinin attaches to host cell’s sialic-acid receptors The influenza virions is then internalized in endosome where the viral M2 proton channel leads to uncoating of the virus The virus genetic material is released, replicated, and the virus is assembled At the end: viral budding: Virus is cleaved by the sialidase activity of NA proteins. The virion is then released from the cell. Virus Drug class Example Influenza A virus M2 inhibitor Amantadine Influenza A & B virus Neuraminidase inhibitor Oseltamivir  Amantadine Mechanism of action: primarily block the M2 proton channel in influenza A leading to: ▪ Early-stage inhibition effect: primarily inhibit the viral M2 proton channel while in the host cell endosome leading to prevention of viral uncoating at early stage ▪ Late-stage inhibition effect: prevention of M2 proton channel also lead to deformation in the HA protein and inhibition of proper viral assembly. ▪ M2 is only in influenza A, thus amantadine is not active against influenza B ▪ useful for the prevention and treatment of infections caused by influenza A virus Side effects: CNS-related side effects (dose-related). The CNS toxic effect can be increased with concomitant administration of antihistamine and anticholinergic drugs. Oseltamivir: Mechanism of action: neuraminidase inhibitor Viral Hemagglutinin is bound to host cell sialic acid on host-cell receptor Virus need to be released by cleaving this bond by viral neuraminidase Inhibition of this neuraminidase lead to inhibition of the viral release The neuraminidase inhibitors are active against many NA in both influenza A and B: Used for treatment of both Influenza A & B. Resistance is less compared to amantadine Side effects: are less toxic than amantadine. GI disturbances (resolve within 1-2days) Anti-hepatitis drugs Hepatitis viruses identified are (A, B, ,C, D). B and C are the most common pathogenic viruses. Hepatitis B virus HBV is a DNA double-stranded virus hepatitis C (HCV) is a single RNA virus  Nucleotide/nucleoside analogues ▪ They require phosphorylation to di- or tri- phosphate for activation. ▪ Some can competitively inhibit: ▪ HBV-related DNA polymerase ▪ Or inhibit HCV-related RNA-dependent-RNA polymerase. ▪ Ribavirin: exerts several mechanism of actions: 1. Monophosphated-ribavirin: inhibit viral GTP synthesis 2. Triphosphate ribavirin: directly inhibits viral mRNA polymerase by acting as nucleotide analogue. 3. It also inhibit the processing of the synthesized mRNA Drug Some side effects Adefovir Nephrotoxicity, hepatomegaly Entecavir Headache, dizziness, fatigue Ribavirin Hemolytic anaemia, teratogenicity Tenofovir Nephrotoxicity, bone loss Interferons Interferons are potent cytokines that possess antiviral, immunomodulatory, and antiproliferative activities. Three major classes of human IFNs: α, β, and γ. Mechanism of action: How does interferon work as antiviral? ❑ The binding of interferon to cell surface receptor molecules signals the cell to produce a series of antiviral proteins leading to several antiviral effects: ❑ Most of these interferons act to inhibit the translation of viral proteins by producing enzymes (methylase and ribonuclease) that degrade the viral mRNA. ❑ INF-a also activate macrophages and other neutrophils and cytotoxic T-lymphocytes to attack the virus. Attachment of IFN proteins to large inert polyethylene glycol (PEG) molecules (pegylation): slows absorption, decreases clearance, and provides higher and more prolonged serum concentrations that enable once weekly dosing. Adverse effects: GI irritation, flu-like symptoms, neutropenia, profound fatigue, alopecia, thyroid dysfunction. Simeprevir: Inhibits the non-structural3/4A protease The NS3/4A protease: essential for generating mature viral proteins required for viral replication, suppress the host antiviral immune system. Adverse effects: anaemia, pruritus, transient increase bilirubin