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Broad spectrum efficacy of BDGR-164 against neurotropic alphaviruses and correlates of protection

ABSTRACT: Broad spectrum efficacy of BDGR-164 against neurotropic alphaviruses and correlates of protection

PROVIDER: PRJNA1076535 | ENA |

REPOSITORIES: ENA

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Broad spectrum efficacy of BDGR-164 against neurotropic alphaviruses and correlates of protection

Project description:Infections by the New World alphaviruses, Eastern Equine encephalitis virus (EEEV), Venezuelan Equine encephalitis virus (VEEV), and Western Equine encephalitis virus (WEEV), cause febrile illness that can progress to fatal disease in humans and equids. Currently there are no FDA-approved antivirals for prophylactic or therapeutic treatment of human infection by these viruses. To combat these infections, we have developed a novel small molecule, BDGR-164, which has subnanomolar potency against VEEV, EEEV, and WEEV. Using an intranasal route of virus infection in a lethal BALB/c model, prophylactic subcutaneous administration of BDGR-164 conferred 100% (VEEV), 88% (EEEV), and 63% (WEEV) survival. To evaluate the ability of BDGR-164 to reduce viral RNA/antigen, inflammation, and pathogenesis, we used RNASeq and histopathology of whole brain at 4 days post-infection (dpi). Viral RNA levels and antigen were reduced significantly in virus-infected and BDGR-164-treated versus virus-infected, sham-treated mice. Moreover, there was a significant reduction in host immune responses associated with inflammatory signaling, immune cell recruitment, and programmed cell death in virus-infected, BDGR-164 treated mice. Cytokine analyses of sera corroborated the reduction in upregulation of the immune response in virus-infected, BDGR-164 treated mice. Limited antiviral resistance to BDGR-164 was detected in one mouse on 4 dpi at NSP2:Y102C. In conclusion, our studies suggest that BDGR-164 has broad and potent prophylactic efficacy against the neurotropic alphaviruses.

2025-01-06 | GSE255795 | GEO

Sinorhizobium medicae strain:164

Project description:Sinorhizobium medicae 164 Resequencing

| PRJNA499363 | ENA

Transcription profiling of human cell lines freely cycling treated with 164 distinct small molecules - Broad Connectivity Map CMAP Set 1

Project description:A reference collection of genome-wide transcriptional expression data for bioactive small molecules. Experiment Overall Design: The current collection (build01) contains data for 164 distinct small molecules applied to freely cycling human cell lines, represented by 453 individual treatment and matched vehicle control pairs.

2008-12-06 | E-GEOD-5258 | biostudies-arrayexpress

Bradyrhizobium japonicum strain:USDA 164 | isolate:USDA 164

Project description:Bradyrhizobium japonicum USDA 164 genome sequencing

| PRJNA1115758 | ENA

Transcriptome sequence of LN229 cells with UM-164 treatment

Project description:Purpose: the goals of this study are to identify the regulated genes of glioma cells by UM-164

2022-11-16 | GSE213586 | GEO

Segatella copri CAG:164

Project description:Prevotella copri CAG:164 overview

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Staphylococcus sp. KFT-164

Project description:Staphylococcus sp. KFT-164 Genome sequencing

| PRJNA862616 | ENA

Novosphingobium clariflavum strain:164

Project description:Novosphingobium clariflavum strain:164 Genome sequencing and assembly

| PRJNA893429 | ENA

Citrobacter freundii strain:164

Project description:Citrobacter freundii strain:164 Genome sequencing and assembly

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The CSF1R-Microglia Axis Has Protective Host-Specific Roles During Neurotropic Picornavirus Infection

Project description:Goal: Determine the role of microglia in the antiviral response during neurotropic picornavirus infection of C57BL/6J and SJL/J mice and whether absence of microglia would affect CD4 and CD8 T cell functions. Methods: Brains from C57BL/6J and SJL/J mice treated with PLX5622 (to deplete microlgia) or control diet were harvested at 6 days post TMEV-infection. CD4+ T cells and CD8+ T cells were obtained using Easy Sep Mouse CD4+ T cell isolation Kit and Easy Sep Mouse CD8+ T cell isolation Kit (Stemcell). RNA was obtained using RNeasy (QIAGEN) and Illumina TruSeq stranded RNA Kit with Ribo-Zero Gold was then utilized to prepare cDNA library for RNA-seq. Results: Our results demonstrate strain-specific effects of the CSF1R-microglia axis in the context of neurotropic viral infection as well as inherent differences in microglial antigen presentation and subsequent T cell crosstalk that contribute to susceptibility to neurotropic picornavirus infection.

2021-05-10 | GSE160660 | GEO

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