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Zika virus (ZIKV) is a flavivirus transmitted by mosquitos that is strongly linked to neurological complications including Guillain-Barré syndrome, meningoencephalitis, and microcephaly. The association between active ZIKV infection during pregnancy and microcephaly and intrauterine growth retardation in the fetus has been confirmed in murine models of ZIKV infection.

Many members of the Flaviviridae family are emerging and reemerging human pathogens that have caused outbreaks of devastating and often fatal diseases and represent a serious public health problem on a global scale. There is no single attenuation strategy that exists which is sufficient to prepare a safe, efficacious and immunogenic live attenuated virus vaccine that will work universally for Flaviviridae.

An arthropod-borne virus, Zika virus (ZIKV), has recently emerged as a major human pathogen. Associated with complications during perinatal development and Guillain-Barré syndrome in adults, ZIKV raises new challenges for understanding the molecular determinants of flavivirus pathogenesis. This underscores the necessity for the development of a reverse genetic system based on an epidemic ZIKV strain. This technology relates to the generation and characterization in cell cultures of an infectious cDNA clone of ZIKV isolated from the 2015 epidemic in Brazil.

Summary – The invention includes compounds and compositions for inhibiting phosphoglycerate mutase (PGM) activity. In some examples, the compounds selectively inhibit cofactor-independent PGM (iPGM). In particular embodiments, the compounds include one or more cyclic peptides.

This application claims live attenuated Zika viruses and vaccines, attenuated chimeric Zika viruses and vaccines, and multivalent immunogenic compositions comprising Zika vaccines and vaccines for other flaviviruses. The chimeric Zika viruses claimed include a first nucleotide sequence encoding at least one structural protein from a Zika virus (ZIKV), a second nucleotide sequence encoding at least one nonstructural protein from a first flavivirus, and a third nucleotide sequence of a 3' untranslated region from a second flavivirus.

The invention relates to compounds that inhibit HIV-1 DNA synthesis mediated by reverse transcriptase (RT). HIV-1 DNA synthesis by RT utilizes deoxynucleoside 5’-triphosphate (dNTP) as substrate and like many other enzymes, the reaction is reversible. Pyrophosphate analogs like imidodiphosphate strongly promote reverse reaction dNTP products containing the imidodiphosphate group instead of the naturally occurring pyrophosphate group. This imidodiphosphate-containing dNTP was found to be a potent inhibitor of the forward RT reaction.

Noroviruses are now recognized as the major cause of non-bacterial gastroenteritis in all age groups, and efforts are underway to develop an effective vaccine. The lack of a robust cell culture system for human noroviruses has complicated vaccine development. Hence, norovirus virus like particles (VLPs) have played an important role in the understanding of virus structure, immune response, antigenic diversity, and vaccine design.

Inhibiting the ability of HIV-1, the virus that causes AIDS, to infect cells is one approach to both prevention and treatment of HIV. Scientists at the NIAID Vaccine Research Center have isolated and characterized neutralizing antibodies (VRC01, 02, 03, and 07) that bind to the CD4 binding site of HIV-1 envelope glycoprotein gp120. These human monoclonal antibodies can potentially be used as a therapeutic to: (1) treat an HIV infection, (2) decrease and prevent HIV-transmission from mother to infant, and (3) be effectively combined with anti-retroviral drug therapy.

Plasmid DNA (clone pNL4-3) that produces infectious HIV-1 virus particles in a wide variety of cells as described in the J Virol. 1986 Aug;59(2):284-91 and developed in the laboratory of Dr. Malcolm Martin at the National Institute of Allergy and Infectious Diseases.