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George Town, Malaysia

Zemla A.,Lawrence Livermore National Laboratory | Kostova T.,Lawrence Livermore National Laboratory | Gorchakov R.,University of Texas Medical Branch | Volkova E.,University of Texas Medical Branch | And 5 more authors.
Bioinformatics and Biology Insights | Year: 2014

A computational approach for identification and assessment of genomic sequence variability (GeneSV) is described. For a given nucleotide sequence, GeneSV collects information about the permissible nucleotide variability (changes that potentially preserve function) observed in corresponding regions in genomic sequences, and combines it with conservation/variability results from protein sequence and structure-based analyses of evaluated protein coding regions. GeneSV was used to predict effects (functional vs. non-functional) of 37 amino acid substitutions on the NS5 polymerase (RdRp) of dengue virus type 2 (DENV-2), 36 of which are not observed in any publicly available DENV-2 sequence. 32 novel mutants with single amino acid substitutions in the RdRp were generated using a DENV-2 reverse genetics system. In 81% (26 of 32) of predictions tested, GeneSV correctly predicted viability of introduced mutations. In 4 of 5 (80%) mutants with double amino acid substitutions proximal in structure to one another GeneSV was also correct in its predictions. Predictive capabilities of the developed system were illustrated on dengue RNA virus, but described in the manuscript a general approach to characterize real or theoretically possible variations in genomic and protein sequences can be applied to any organism. © the authors, publisher and licensee ibertas cademica imited. Source


Hickey A.C.,Boston University | Koster J.A.,Boston University | Thalmann C.M.,Boston University | Hardcastle K.,National Institute of Allergy and Infectious Diseases | And 3 more authors.
American Journal of Tropical Medicine and Hygiene | Year: 2013

Dengue virus (DENV) is considered to be the most important arthropod-borne viral disease and causes more than 100 million human infections annually. To further characterize primary DENV infection in vivo, rhesus macaques were infected with DENV-1, DENV-2, DENV-3, or DENV-4 and clinical parameters, as well as specificity and longevity of serologic responses, were assessed. Overt clinical symptoms were not present after infection. However, abnormalities in blood biochemical parameters consistent with heart, kidney, and liver damage were observed, and changes in plasma fibrinogen, D-dimers, and protein C indicated systemic activation of the blood coagulation pathway. Significant homotypic and heterotypic serum immunoglobulins were present in all animals, and IgG persisted for at least 390 days. Serum neutralizing antibody responses were highly serotype specific by day 120. However, some heterotypic neutralizing activity was noted in infected animals. Identification of serotype-specific host responses may help elucidate mechanisms that mediate severe DENV disease after reinfection. Copyright © 2013 by The American Society of Tropical Medicine and Hygiene. Source


Patent
Sentinext Therapeutics Sdn Bhd | Date: 2014-08-20

The instant invention provides materials and methods for producing immunologically active antigens derived from members of the Picornaviridae virus family. The picornavirus antigens of the invention may be in a form for use as a vaccine administered to a subject in a therapeutic treatment or for the prevention of a picornavirus infection. The picornavirus antigens of the invention may be in the form of an immunogenic composition for use in vaccines which are administered for the prevention of an Enterovirus infection. The instant invention further encompasses immunogenic compositions comprising Human enterovirus A, Human enterovirus B, Human enterovirus C, Human enterovirus D antigens and their use in vaccines for the prevention of an Enterovirus infection.


Patent
Sentinext Therapeutics Sdn Bhd | Date: 2012-11-01

The instant invention provides materials and methods for producing immunologically active antigens derived from members of the Picornaviridae virus family. The picornavirus antigens of the invention may be in a form for use as a vaccine administered to a subject in a therapeutic treatment or for the prevention of a picornavirus infection. The picornavirus antigens of the invention may be in the form of an immunogenic composition for use in vaccines which are administered for the prevention of an Enterovirus infection. The instant invention further encompasses immunogenic compositions comprising Human enterovirus A, Human enterovirus B, Human enterovirus C, Human enterovirus D antigens and their use in vaccines for the prevention of an Enterovirus infection.


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Sentinext Therapeutics Sdn Bhd | Date: 2010-02-03

Antivirals; Vaccines.

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