Zanamivir: from drug design to the clinic

Abstract

The development of the neuraminidase inhibitors has revolutionized the management options for in£u-enza. Zanamivir was the ¢rst such inhibitor to be approved for the treatment of in£uenza in humans. It is delivered by inhalation to the respiratory tract, which is the site of viral replication, in order to ensure immediate antiviral activity. Early treatment with zanamivir in clinical trials rapidly reduced the severity and duration of in£uenza symptoms and associated complications. Furthermore, chemoprophylaxis with zanamivir was shown to be e¡ective in the prevention of in£uenza illness. To date, there is no evidence for the emergence of clinically signi¢cant zanamivir-resistant isolates. In conclusion, zanamivir o¡ers a useful complementary strategy to vaccination in the e¡ective management of in£uenza.

Structure and Functions of Influenza Virus Neuraminidase

“…Recently, NA has become a 'hot' target in anti-influenza fields and newly discovered drugs, zanamivir (Relenza ® ) [56] and oseltamivir (Tamiflu ® ) [57], are all the NAIs. So in this article we will mainly discuss NA of the influenza virus.…”

Development of Influenza Virus Sialidase Inhibitors

“…4-Deoxy-4-guanidino-Neu5Ac2en 5 was selected by Glaxo in 1990 as a lead drug candidate against influenza virus infection, and progressed under the generic name zanamivir (reviewed in [130,131]). Zanamivir was granted regula tory approval by the Food and Drug Administration (FDA) in the United States in 1999, under the tradename Relenza, as the first sialidase-targeting drug for the treatment of influenza.…”

Zanamivir Oral Delivery: Enhanced Plasma and Lung Bioavailability in Rats

“…Influenza is a highly contagious respiratory tract infection that is caused by influenza type A and B viruses (Elliott, 2001). Influenza can cause serious morbidity and increased mortality, particularly in the elderly or the immunocompromised and those with underlying diseases such as chronic obstructive pulmonary disease, cardiovascular disease, and diabetes (Dunn and Goa, 1999; Freund et al ., 1999; Elliott, 2001; Colman, 2005).…”

“…Influenza can cause serious morbidity and increased mortality, particularly in the elderly or the immunocompromised and those with underlying diseases such as chronic obstructive pulmonary disease, cardiovascular disease, and diabetes (Dunn and Goa, 1999; Freund et al ., 1999; Elliott, 2001; Colman, 2005). Neuraminidase inhibitors, oseltamivir and zanamivir (ZMR), are considered to be the drug of choice in the treatment of influenza principally due to their low toxicity and high efficacy (Freund et al ., 1999; Boonyapiwat et al ., 2011; Gupta et al ., 2011).…”

“…1) is available as a dry powder formulation for oral inhalation applied using Diskhaler™ (a dry powder inhaler) due to its poor oral bioavailability (2%; range 1 to 5%) in human (Dunn and Goa, 1999; Caballero et al ., 2000; Elliott, 2001; Colman, 2005). The major drawback with this route of administration is lack of patient compliance, and therapy is not recommended in patients with chronic represpiratory conditions such as asthma, COPD, etc.…”