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Inhibitors of Other Viruses

Inhibitors of Other Viruses. RIBAVIRIN Ribavirin (Virazole) is a nucleoside analogue in which a triazolecarboxamide moiety is substituted on place of the normal purine precursor aminoimidazolecarboxamide ** The drug inhibits the synthesis of guanine nucleotides, which

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Inhibitors of Other Viruses

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  1. Inhibitors of Other Viruses • RIBAVIRIN Ribavirin (Virazole) is a nucleoside analogue in which a triazolecarboxamide moiety is substituted on place of the normal purine precursor aminoimidazolecarboxamide ** The drug inhibits the synthesis of guanine nucleotides, which are essential for both DNA and RNA viruses.

  2. - Ribavirin aerosol is used clinically to treat pneumonitis caused by respiratory syncytial virus in infants and to treat severe influenza B infections. B. ADEFOVIR Adefovir (Hepsera) is a nucleotide analogue of adenosine monophosphate that inhibits the DNA polymerase of hepatitis B virus. It is used for the treatment of chronic active hepatitis caused by this virus.

  3. C. Entecavir • Entecavir ( baraclude ) is guanosine analogue that inhibits the DNA polymerase of hepatitis B virus (HBV) . • It has no activity against the DNA ( reverse transcriptase ) of HIV. • Its approved for the treatment of adults with chronic HBV infection .

  4. INHIBITION OF CLEAVAGE OF PRECURSOR POLYPEPTIDES Several drugs, such as saquinavir (Invirase, Fortovase), indinavir (Crixivan), ritonavir (Norvir), amprenavir (Agenerase), and nelfinavir (Viracept), are inhibitors of the protease encoded by HIV . These inhibitors contain peptide bonds that bind to the active site of the viral protease, thereby preventing the protease from cleaving the viral precursor.

  5. These drugs inhibit production of infectious virions but do not affect the proviral DNA and therefore do not cure the infection. The effect of protease inhibitors on the replication of HIV is depicted in the next Figure - Virion: A complete virus particle with its DNA or RNA core and protein coat as it exists outside the cell. Also called a viral particle.

  6. Monotherapy with protease inhibitors should not be used because resistant mutants emerge rapidly. • These drugs are prescribed in combination with reverse transcriptase inhibitors, either nucleoside analogues such as zidovudine and lamivudine or non-nucleoside inhibitors such as nevirapine.

  7. The side effects of protease inhibitors include nausea, diarrhea, and abnormal fat accumulation in the back of the neck that can result in a "buffalo hump" appearance. The metabolic process by which this occurs is unknown. - Indinavir can cause kidney stones; thus, extra water should be consumed to reduce the likelihood of stone formation. - Ritonavir can cause circumoral paresthesias.

  8. INHIBITION OF VIRAL PROTEIN SYNTHESIS • INTERFERON The mode of action of interferon is discussed in Chapter 33 with dr. Ali Shaaban Recombinant alpha interferon is effective in the treatment of some patients with chronic hepatitis B and chronic hepatitis C infections. It also causes regression of condylomata acuminata lesions caused by human papillomavirus and the lesions of Kaposi's sarcoma caused by human herpesvirus-8.

  9. Pegylated interferon (Peg-intron), which is interferon alpha conjugated to polyethylene glycol, is available for the treatment of chronic hepatitis C. B. FOMIVIRSEN Fomivirsen (Vitravene) is an andsense DNA that blocks the replication of CMV.

  10. - Antisense DNA is a single-stranded DNA whose base sequence is the complement of the viral mRNA. - Antisense DNA binds to the mRNA within the infected cell and prevents it from being translated into viral protein. - Fomivirsen is approved for the intraocular treatment of CMV retinitis. It is the first and, at present, the only antisense molecule to be approved for the treatment of human disease.

  11. C. METHISAZONE • Methisazone • (N-methylisatin-β-thiosemicarbazone) specifically inhibits the protein synthesis of poxviruses, such as smallpox and vaccinia viruses, by blocking the translation of late mRNA.

  12. INHIBITION OF RELEASE OF VIRUS • Zanamivir (Relenza) and oseltamivir (Tamiflu) inhibit the neuraminidase of influenza virus. This enzyme is located on the surface of influenza virus and is required for the release of the virus from infected cells. • Inhibition of release of influenza virus limits the infection by reducing the spread of virus from one cell to another.

  13. These drugs are effective against both influenza A and B viruses, in contrast to amantadine, which is effective only against influenza A virus. • These drugs are effective against strains of influenza virus resistant to amantadine.

  14. CHEMOPROPHYLAXlS • In most instances, the antiviral agents described in this chapter are used to treat infectious diseases. However, there are times when they are used to prevent diseases from occurring, a process called chemoprophylaxis. Table 35-2 describes the drugs used for this purpose

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