Week 10

(1)

Week 10

Antiviral

(2)

• Viruses - obligate intracellular microorganisms

• Utilize- host metabolic enzymes and ribosomes for protein synthesis

• Drugs for viruses must penetrate host cells.

• Might negatively impact normal pathways of the host

• Narrow therapeutic index compared to antibacterials

(3)

• Interfere with

• viral nucleic acid synthesis

• Regulation

• viral cell binding- attachment/penetration (antiviral antibodies-gamma globulin)

• virus uncoating (interferon, amantadine, rimantadine)

• metabolic pathways

• Early translation-fomivirsen

• Transcription- inhibitors of DNA polymerase, Inhibitors of RNA dependent DNA polymerase

• nucleic acid analogs - RNA and DNA production.

• Inhibition of single steps in the viral replication – virustatic (temporary)- needs host immune response.

(4)

• Nucleoside reverse transcriptase inhibitors (NRTIs)

• Non-nucleoside reverse transcriptase inhibitors (NNRTIs)

• Protease inhibitors (PIs)

• Integrase inhibitors (INSTIs)

• Fusion inhibitors (FIs)

• Chemokine receptor antagonists (CCR5 antagonists)

(5)

Nucleoside reverse transcriptase inhibitors- (NRTI)

• Block reverse transcriptase

• This enzyme reverse transcriptase to convert its RNA into DNA (reverse transcription)

• HOW? Activated- phosphorylation to the triphosphate form by

cellular enzymes- competes with cellular triphosphates, which are substrates for proviral DNA by viral reverse transcriptase.

(6)

NRTI

• Entecavir

• Abacavir

• Tenofovir

• Adefovir

• Lamivudine

• Zidovudine

• Telbivudine

• Stavudine

• Emtricitabine

• Didanosine

(7)

Non-nucleoside reverse transcriptase inhibitors (NNRTIs)- Non-nukes

• Binding directly to the enzyme- at a site different from the nucleoside binding component- cause an allosteric inhibition of the transcriptase

• Nevirapine

• delavirdine

• efavirenz

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Protease inhibitors

• Synthetic drugs - inhibit the action of HIV-1 protease (cleaves two precursor proteins into smaller fragments)- necessary for viral

growth, infectivity and replication.

• Bind to the active site of the protease enzyme - prevent the maturation of the newly produced virions – making them non- infectious.

(9)

Protease inhibitors

• Boceprevir

• Simeprevir

• Fosamprenavir

• Lopinavir

• Darunavir

• Telaprevir

• Tipranavir

• Ritonavir

• Arazanavir

• Nelfinavir

• Indinavir

• Saquinavir

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Integrase inhibitors (INIs)

• Block the action of integrase, a viral enzyme that inserts the viral genome into the DNA of the host cell.

• Dolutegravir

• Elvitegravir

• Raltegravir

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Fusion inhibitors

• Blocking cognate virus–receptor interactions is the most obvious antiviral paradigm for entry inhibitors- maraviroc- CC chemokine receptor 5 (CCR5)

• cholesterol and unsaturated phospholipids can increase and decrease membrane rigidity

• maraviroc

• enfuvirtide

(12)

CCR5 inhibitors

• Prevent- CD4 T-cells by blocking the CCR5 receptor- Maraviroc

•

• When the CCR5 receptor is unavailable, tropic site cannot engage with a CD4 T-cell to infect the cell.

• Aplaviroc

• Vicriviroc

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• Anionic polymer

Virus attachment to the host cell

• Chemokine receptor inhibito, CD4 inhibitör, Enfuvirtide

Virus entry

• NRTI

• NNRTI

Reverse transcription

• Integrase inhibitors

Integration of viral DNA into host genome Trasncription and translation

• PIs

Proteolytic processing of viral proteins Budding of new virüs particles

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• Foot and Moth Disease

• antiviral treatment in a vaccinated zone could protect against viral dissemination and fill the time gap between vaccination and the development of protective immunity.

• ribavirin, 2 -C-methylcytidine, pyrazinecarboxamide ′ ′

• Immunomodulators such as IFN

• Acyclic nucleoside phosphonates- cidofovir

• Feline herpesvirus1- Aciclovir, ganciclovir and penciclovir are acyclic nucleoside, recombinant feline IFN-ω

• Feline retrovirus- IFN

• Canine viral- feline IFN-ω is licensed for use in dogs with CPV-2 (canine parvoviral) clinical infection