Novel Carbohydrate-Based Inhibitors That Target Influenza A Virus Sialidase

Abstract

Influenza virus continues to cause significant morbidity and mortality despite the fact that both anti-influenza viral drugs and vaccines to the current circulating strains are available [1, 2]. In terms of anti-influenza drug development, the surface-oriented viral enzyme sialidase (neuraminidase, NA), which plays a major role in the virus life cycle by facilitating release of virus progeny from the infected cell [3], has proven a successful target for the development of clinically useful drugs [4, 5]. Potent and selective inhibitors of the viral sialidase, such as zanamivir (1, Relenza) and oseltamivir carboxylate (OC, 2; the active form of oseltamivir 3, Tamiflu), the two widely used anti-influenza drugs, efficiently block viral sialidase activity resulting in virus progeny remaining clumped at the infected cell’s surface [6] and, consequently, limitation of the spread of infection. The phenomenon of resistance development to drugs-in-use, however, is a continuing issue [7], and applies to both zanamivir and oseltamivir. Oseltamivir, the most used anti-influenza drug, has suffered significant loss of efficacy as a result of drug resistance during the past 4 years [7].