Conformationally locked sugar derivatives and analogues as potential neuraminidase inhibitors

The influenza virus remains a major health concern for mankind because it tends to mutate frequently and cause high morbidity. Influenza prevention and treatment are greatly aided by the use of antivirals. One such class of antivirals is neuraminidase inhibitors (NAIs), effective against influenza viruses. A neuraminidase on the virus's surface serves a vital function in viral propogation by assisting in the release of viruses from infected host cells. Neuraminidase inhibitors are the backbone in stoping such virus propagation thus helps in the treatment of influenza viruses infections. Two NAI medicines are licensed globally: Oseltamivir (Tamiflu™) and Zanamivir (Relanza™). There are two molecules that have acquired Japanese approval recently: Peramivir and Laninamivir, whereas Laninamivir octanoate is in Phase III clinical trials. The need for novel NAIs is due to frequent mutations in viruses and the rise in resistance against existing medication. The NA inhibitors (NAIs) are designed to have (oxa)cyclohexene scaffolds (a sugar scaffold) to mimic the oxonium transition state in the enzymatic cleavage of sialic acid. This review discusses in details and comprises all such conformationally locked (oxa)cyclohexene scaffolds and their analogues which have been recently designed and synthesized as potential neuraminidase inhibitors, thus as antiviral molecules. The structure-activity relationship of such diverese molecules has also been discussed in this review.