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Antiviral Agents

Antiviral Agents

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Published by Kate Mendoza

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Published by: Kate Mendoza on Sep 28, 2011
Copyright:Attribution Non-commercial

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 Viruses-
 
Obligate intracellular parasites-
 
Replication depends primarily on synthetic processes of the host cellViral Replication Steps1.
 
Attachment of the virus to the host cell2.
 
Entry of the virus through the host cell membrane3.
 
Uncoating of viral nucleic acid4.
 
Synthesis of early regulatory proteins5.
 
Synthesis of RNA or DNA6.
 
Synthesis of late, structural proteins7.
 
Assembly (maturation) of viral particles8.
 
Release from the cellANTIVIRAL AGENTS-
 
Progress in antiviral chemotherapy began in the
early 1950’s, when the search for anticancer drugs
generated several new compounds capable of inhibiting viral DNA synthesis.-
 
First-generation antiviral agents: (poor specificity that rendered them too toxic for systemic use, buteffective when used topically for treatment of herpes keratitis)
o
 
5-iododeoxyuridine
o
 
Trifluorothymidine
 
To be EFFECTIVE, antiviral agents must:
o
 
block viral entry/exit from the host cell
o
 
be active inside host cell
 
To be IDEAL, antiviral agents must be:
o
 
selective (no damage to host cell)
o
 
reduce symptom w/o affecting immune response
 
NEED for agents vs. viruses
o
 
Vaccine not available
o
 
Multiple serotypes ( e.g. rhinoviruses)
o
 
Constantly changing (e.g. influenza, HIV)
 
ANTIVIRAL AGENTS
Subject: PharmacologyTopic: Antiviral AgentsLecturer: Dr. Deo PanganibanDate of Lecture: Sept 16, 2011Transcriptionists: Neneng Balentong
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 Antiviral agents canpotentially target anyof these steps
 
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Major Sites of Antiviral drug action:
Note: Interferon-alfa are speculated to have multiple sites of action
Pathogenic Viruses
o
 
DNA Viruses
- poxvirus, herpes virus, adenovirus, papilloma virus*enter host cell nucleus and direct the generation of new viruses
o
 
RNA Viruses
- orthomyxovirus, rubella, rhabdovirus, picornavirus, retrovirus, arenavirus, hepadnavirus,arbovirus*does not involve host cell nucleus
o
 
RNA Retroviruses
:
 
AIDS virus
 
T-cell leukemia virus*contain an enzyme, reverse transcriptase, which makes a DNA copy of the viral RNA. This DNAcopy is integrated into the host cell genome and directs the generation of new virus particles.
 
Possible Site/s of Antiviral Action
o
 
Attachment to host cells (gammaglobulin)
o
 
Uncoating (Amantadine)
o
 
Synthesis of viral mRNA (Interferons)
o
 
Translation of mRNA (Interferons)
o
 
Replication of viral RNA or DNA(Nucleoside Analogues)
o
 
Maturation of new virus proteins(Protease Inhibitors)
o
 
Release
 
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 A.
Inhibition of transcription of the viral genome
1. DNA polymerase inhibitors* Acyclovir, Valacyclovir, Famciclovir2. Antiretroviral agents*NRTI- AZT (NRTI= Nucleoside Reverse Transcriptase Inhibitor; AZT= Zidovudine)*NNRTI-Nevirapine (NNRTI=Nonnucleoside Reverse Transcriptase Inhibitor)
B. Inhibition of post-translational events
1. Protease Inhibitors*Saquinavir
C. Inhibition of attachment to or penetration of host cells
*Amantadine
D. Immunomodulators
1. Interferons
 
Herpes simplex 
- Acyclovir
 
Varicella-Zoster 
- Acyclovir
 
Cytomegalovirus
- Gancyclovir, Foscarnet
 
 AIDS
- AZT, 3TC, Protease inhibitors combination (AZT= Zidovudine; 3TC= Lamivudine)
 
Respiratory Syncythial 
 
Virus
- Ribavirin
 
Influenza
 
 –
AmantadineNucleoside Analogs
 
Synthetic compounds that resemble nucleosides but have an incomplete or abnormal deoxyribose/ribosegroup
 
Phosphorylated to the tri-phosphate form within the infected cells---compete with normal nucleotidesfor incorporation into viral DNA or RNA >>>irreversible inhibition of viral polymerase and chaintermination
 
NUCLEOSIDE ANALOGSGENERAL ACTIONS OF ANTIVIRAL DRUGSViruses responsive to Antiviral Agents

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