Yellow Fever Virus Cell Lysate (17D)

The Flavivirus genus of the Flaviviridae family Includes 70 enveloped single-stranded-RNA positive-sense viruses transmitted by arthropods Among these viruses there are a relevant number of human pathogens including the mosquito-borne dengue virus (DENV) yellow fever virus (YFV) Japanese encephalitis virus (JEV) and West Nile virus (WNV) as well as tick-borne viruses such as tick-borne encephalitis virus (TBEV) Langat virus (LGTV) and Omsk hemorrhagic fever (OHFV) The flavivirus envelope (E) protein is a dominant antigen inducing immunologic responses in Infected hosts and eliciting virus-neutralizing antibodies The domain III (DIII) of E protein contains a panel of Important epitopes that are recognized by virus-neutralizing monoclonal antibodies Peptides of the DIII have been used with promising results as antigens for flavivirus serologic diagnosis and as targets for immunization against these viruses We review here some important aspects of the molecular structure of the DIII as well as its use as antigens for serologic diagnosis and immunization in animal models (C) 2010 The International Association for Biologicals Published by Elsevier Ltd All rights reserved

A series of pyrazinecarboxamide derivatives T-705 (favipiravir), T-1105 and T-1106 were discovered to be candidate antiviral drugs. These compounds have demonstrated good activity in treating viral infections in laboratory animals caused by various RNA viruses, including influenza virus, arenaviruses, bunyaviruses, West Nile virus (WNV), yellow fever virus (YFV), and foot-and-mouth disease virus (FMDV). Treatment has in some cases been effective when initiated up to 5-7 days after virus infection, when the animals already showed signs of illness. Studies on the mechanism of action of T-705 have shown that this compound is converted to the ribofuranosyltriphosphate derivative by host enzymes, and this metabolite selectively inhibits the influenza viral RNA-dependent RNA polymerase without cytotoxicity to mammalian cells. Interestingly, these compounds do not inhibit host DNA and RNA synthesis and inosine 5'-mono phosphate dehydrogenase (IMPDH) activity. From in vivo studies using several animal models, the pyrazinecarboxamide derivatives were found to be effective in protecting animals from death, reducing viral burden, and limiting disease manifestations, even when treatment was initiated after virus inoculation. Importantly, T-705 imparts its beneficial antiviral effects without significant toxicity to the host. Prompt development of these compounds is expected to provide effective countermeasures against pandemic influenza virus and several bioweapon threats, all of which are of great global public health concern given the current paucity of highly effective broad-spectrum drugs. (C) 2009 Elsevier B.V. All rights reserved.