Ribavirin

Overview

Ribavirin was first synthesized in 1970 by ICN Pharmaceuticals (now “Valent International Pharmaceuticals”). In 1986, its first major use was the treatment of RSV (respiratory syncitial virus) infections in pediatric patients, but since its FDA approval in 1998, it has primarily been used as a component in treating Hepatitis C. The treatment was modified and approved in 2002 by the FDA by combining it with interferon alfa2b. ^[1]

Structure & Function

While the main function of Ribavirin is to treat Hepatitis C and RSV, Ribavirin alone is not enough to treat these diseases and is commonly combined with interferon alfa2b. Ribavirin contains antiviral activity which inhibits DNA/RNA synthesis.The structure of Ribavirin resembles the structure of the nucleoside guanosine. Like guanosine, ribavirin is also water soluble and is able to mimic other purines as well. However, a key difference between the structure of ribavirin and the purine nucleosides is that it’s heterocyclic base contains only one ring, as opposed to purines which have two. Despite this, it is able to go through similar mechanisms as that of nucleosides such as phosphorylating into a triphosphate. It’s structural similarity to the common nucleoside guanosine may suggest how the drug can inhibit DNA/RNA synthesis through purine mimicry.

Disease

Hepatitis C

Hepatitis C is an infectious disease that affects the liver due to the Hepatitis C virus (HCV). This disease can be acute or chronic and can even lead to death. By binding to the gC1qR receptor, HCV proteins are able to effectively inhibit the differentiation of helper T cells. In addition, HCV core proteins work by preventing the synthesis of the antiviral interferon IFN-γ. Thus, weakening the body’s immunity and making it susceptible to infection. Ribavirin is used in combination with peginterferon to treat Hepatitis C.^[2] By adding pegylated interferon-alpha to ribavirin, the drug had a longer half life, which required only single weekly dosing for Hepatitis C treatment. ^[3] Polyethylene glycol (PEG) is covalently attached with two types:1. P-INFa-2b and 2. P-INFa-2a. While P-INFa-2b is linear and subject to hydrolysis upon injection, P-INFa-2a is branched and circulated the molecule as a whole. The limited distribution of P-INFa-2a results in a longer half life. ^[4]

Pneumonia

Respiratory syncytial virus is responsible for viral pneumonia. This infection causes the air sacs in one or both of the lungs to become inflamed and potentially filled with fluid or pus. In infants, children, and adults over the age of 65, pneumonia can be deadly. It has been shown that Ribavirin can treat viral pneumonia by preventing transcription of respiratory syncytial virus. ^[5]

Mechanism

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