Antiviral drugs interferon

A. Oseltamivir inhibits neuraminidase, an enzyme that cleaves neuraminic acid from oligosaccharides. Neuraminidase activity aids the movement of viral particles through neuraminic acid-rich respiratory secretions and is required for the release of progeny virions. Inhibition of viral DNA polymerase is the mechanism of action of nucleoside analogue antiviral drugs. Interferons do stimulate the JAK-STAT signaling pathway but do not stimulate proliferation of immune cells. Ribavirin inhibits GTP synthesis, and the antiretroviral protease inhibitors (e.g., ritonavir) inhibit HIV protease. 

Drug therapy is used to suppress viral replication by immune mediating or antiviral effects. Interferon 2b lbN-fb1 lamivudine, telbivudine, ade-fovir entecavir, and pegylated IFN-a2a (PEG-IFN) are approved in the United States for first-line treatment of chronic HBV. 

The major sites of antiviral drug action. Note Interferon alfas are speculated to have multiple sites of action. 

A severe acute flare of porphyria cutanea tarda has been reported in a 61-year-old man after 4 months of treatment with interferon alfa-2b plus ribavirin for chronic hepatitis C (553). No further relapse was observed after chloroquine treatment, despite continuation of the antiviral drugs. 

Becker, Yechiel, ed. (1984). Antiviral Drugs and Interferon The Molecular Basis of Their Activity. New York Kluwer. 

Though interferon was first reported in 1957 by Issacs and Lindenmann but it was recognized as an antiviral drug in 1980. 

There is no established course of treatment for patients infected with RVF virus. However, studies in monkeys and other animals have shown promise tor ribavirin, an antiviral drug, for future use in humans. Additional. studies suggest that interferon, immune modulators, and convalescent-phase plasma may also help in the treatment of patients with RVF. 

Systematic reviews In a systematic review of antiviral drug therapy in 16 studies, in which pegylated interferon alfa was used in combination with ribavirin for recurrent hepatitis C after liver transplantation, the mean sustained viral response rate was 30% (range 8-50%) [34 ]. Dosage reduction and withdrawal of treatment were common (73% and 28% respectively). 

A quite different approach to antiviral drugs is to seek small molecules which can stimulate the formation of interferon in the host. Interferon is a small protein whose production in the human body is normally stimulated by the presence of a virus, and which causes the host cell to produce an antiviral protein. Human interferon is non-toxic to man and has a broad spectrum of antiviral activity. Small, and inadequate supplies can be obtained from the pooled leucocytes of blood banks. Interferon from other mammals is ineffective in man. Although polynucleotides and some other... 

Interferon-a2b has diverse mechanisms of action, including antiviral activity, impact on cellular metabolism and differentiation, and antitumor activity.42 The antitumor activity is due to a combination of direct antiproliferative effect on tumor cells and indirect immune-mediated effects.42 Interferon-a2b is currently approved by the Food and Drug Administration (FDA) as adjuvant therapy for patients who are free of disease after curative surgical resection but are at high risk of MM recurrence. This includes patients with bulky disease or regional lymph node involvement such as stage IIB, IIC, or III disease.43 It is controversial if interferon-a2b (IFN) should be offered as adjuvant therapy for every high-risk MM patient. The reason is because clinical trials with different doses of IFN have not proved definitively that IFN improves overall patient survival. 

Mechanism of Action. Although the details are unclear, imiquimod enhances the local production of interferons, tumour necrosis factor-alpha, and possibly other cytokines that produce antiviral responses. Hence, this drug does not act directly on the virus, but instead modulates the host (human) immune responses that have antiviral effects. 

Antiviral Efficacy and Clinical Use. Ribavirin (Vira-zole) is active against several RNA and DNA viruses, including respiratory syncytial virus (RSV).106 Clinically, this drug is used to treat severe RSV pneumonia in infants and young children,106 and RSV in certain adult populations, including the elderly, people with cardiopulmonary problems, and people with a compromised immune system.29 Ribavirin may also be useful as a secondary agent in the treatment of influenza A and B in young adults. The combination of ribavirin and interferons (see section on Interferons, later) is often the treatment of choice in chronic hepatitis C infection.30 72... 

The possibility that interferons can be used as pharmacologic agents has aroused a great deal of interest. Recombinant DNA techniques and cell tissue cultures have been used to produce sufficient quantities of interferons for clinical drug trials. The rationale is that exogenously administered interferons will produce antiviral and other beneficial effects in healthy cells in a manner similar to their endogenously produced counterparts. Some of the pertinent aspects of interferon action and clinical applications are presented below. 

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