Imino sugars, such as deoxynojirimycin (DNJ), are glucose analogues that selectively inhibit cellular .alpha.-glucosidase I and II (enzymes that process N-linked glycans in glycoprotein) and exhibit broad spectrum antiviral activities against many enveloped viruses. Previously we have reported a novel DNJ derivative, OSL-95II, with antiviral activity and reduced cytotoxicity. In order to develop imino sugars with more potent antiviral activity as well as improved toxicity profile, OSL-95II was modified by diversifying the nitrogen linked alkylated side chain. The antiviral activities were initially tested in bovine viral diarrhea virus (BVDV) infected MDBK cells, yielding several imino sugar derivatives with novel structure and superior antiviral activity and toxicity profile. Furthermore, these new compounds were shown to be active against Dengue virus (DV) and West Nile virus (WNV) infection in BHK cells where potent anti-DV activity having submicromolar EC50 values and SI of greater than 900. These compounds represent a new generation of iminio sugars and their analogues, having application in the clinical treatment of infection of DV and other members of flaviviridae.

Block; Timothy M.

Chang; Jinhong

Xu; Xiaodong

Baruch S. Blumberg Institute

Drexel University

Imino sugar derivatives demonstrate potent antiviral activity and reduced toxicity

The present invention provides a compound of formula A: ##STR00001## or a pharmaceutically acceptable salt thereof, wherein B, Q, R.sup.1, R.sup.5, R.sup.6, R.sup.7, R.sup.8 and Z are as defined herein, which is a 2'-branched nucleoside useful for the treatment or prevention of viral infections, particularly dengue fever, yellow fever, West Nile virus, Japanese encephalitis virus, tick-borne encephalitis virus, Kunjin virus, Murray Valley encephalitis, St Louis encephalitis, Omsk hemorrhagic fever virus, bovine viral diarrhea virus, Zika virus and Hepatitis C virus.

Anandan; Sampath-Kumar

Aulakh; Virender Singh

Fenaux; Martijn

Lin; Xiaodong

Mao; Liang

Saunders; Oliver

Sweeney; Zachary Kevin

Yokokawa; Fumiaki

Zhong; Weidong

Novartis AG

2'-Ethynyl nucleoside derivatives for treatment of viral infections

The present invention provides a compound of formula A: ##STR00001## or a pharmaceutically acceptable salt thereof, wherein B, Q, R.sup.1, R.sup.5, R.sup.6, R.sup.7, R.sup.8 and Z are defined herein, which is a 2'-branched nucleoside useful for the treatment or prevention of viral infections, particularly dengue virus, yellow fever virus, West Nile virus, Japanese encephalitis virus, tick-borne encephalitis virus, Kunjin virus, Murray Valley encephalitis, St Louis encephalitis, Omsk hemorrhagic fever virus, bovine viral diarrhea virus, Zika virus and Hepatitis C virus.

2'-ethynyl nucleoside derivatives for treatment of viral infections

The invention is a vaccine, and method of vaccination, against RNA viruses, including RNA viruses in the family Flaviviridae, which includes for example West Nile Virus, Yellow fever virus, Dengue fever virus, Hepatitis C virus, Pestiviruses, Bovine viral diarrhea virus, and Classical Swine fever virus, wherein the vaccine comprises the RNA virus or immunogenic portions thereof, which have been treated with and rendered non-pathogenic by a phenothiazine dye and visible light. The invention includes novel strains of WNV for use in producing a vaccine.

dengue/diarrea

Imino sugar derivatives demonstrate potent antiviral activity and reduced toxicity

2'-Ethynyl nucleoside derivatives for treatment of viral infections

2'-ethynyl nucleoside derivatives for treatment of viral infections

RNA virus vaccines and methods

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