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Description

Virus Structure: - Nucleic acid, Capside, spikes, envelope - Complex, Helical, Icosahedral (HIV) - Single stranded, Double stranded - Reverse Transcriptase (RT) - (+) = sense-stranded RNA can serve as mRNA directly to host cell - (-) = antisense-stranded first transcribe the + , virus contain an RNA transcriptase.

Treatment of Influenza M2 channel inhibitors: Amantadine and Rimantadine - Tricyclic amines - M2 only found in Influenza A (not effective vs Influenza B) - Blocks H+ entry into virus particle, needed for acidification. - Prevents uncoating therefore cant release particle in host to replicate Neuraminidase inhibitors Oseltamivir, Zanamine, Peramivir - Sialic acid mimics - Influenza virus have two surface glycoprotein’s neuraminidase (NA) - Inhibit NA that cleaves a sialic acid bond to release the synthesized virus from the host cell. - One bond cleaved between sialic acid and Galactose - Prevents release therefore virus cant spread - Oseltamivir PRODRUG hydrolyzed into CA. - Zan & Pera ZWITTERions neutral have both CA & Guanidine structure ) Polymerase Acidic Endonuclease Inhibitors Baloxavir - Inhibits cap snatching - Viruses to hijack the host mRNA transcription system to allow synthesis of viral RNAs. - Cap snatching: first 10-20 residues of a host cell RNA is removed (snatched) and used as the 5' cap of the viral RNA - Prevents Translation - Baloxavir PRODRUG Oxidative O-dealkylation

Treatment of Herpes Simplex I/II, Chicken Pox, CMV, Hepatitis B Virus use same building blocks as humans (DNA/RNA) nucleotides - Agents that interfere with viral nucleic acid replication: DNA polymerase inhibitors Acyclovir,Valacyclovir acyclic nucleosides. - Drug resemble nucleic acid, but dont have 3’ end therefore stops growing chain - DNA Polymerase is an enzyme that can copy DNA molecules. Nucleotides are added to the 3’OH of the sugar - PRODRUGs: Valacyclovir, Valganiclovir, Famciclovir - Valacyclovir has Inactive metabolite Suspected neuropsychiatric side effects Reverse Transcriptase inhibitor for HepB Adefovir dipivoxil , Cidofovir , Foscarnet: - Binds to DNA polymerase (by acting like pyrophosphate) preventing cleavage of the pyrophosphate of growing chain. - Adefovir dipivoxil PRODRUG activated by Esterase (phosphorylated), and Adenylate Kinase (diphosphorylted) Conventional Nucleosides

Treatment of Hepatitis C +RNA that codes for 10 polypeptides: Structural proteins: 2 envelope proteins E1 and E2 Non-structural proteins: NS2, NS3, NS4A, NS4B, NS5A and NS5B NS3/4A Protease Inhibitors- all contain Proline

NS5A Protease Inhibitors - Symmetrical , Imidazole, N-acyl Pyrrole

NS5B Protease Inhibitors Nucleoside: - Prodrugs, needs to be metabolized to the triphosphate - Unnatural sugar - Sofosbuvir, Mericitabine Non- Nucleoside - Dasabuvir - Has 10 Metabolites; Omega Oxidation & Oxidative O-Demethylation - Alkenes goes under Reduction...