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Effective disinfection of Ebola virus (EBOV) in body fluids is critical for emergency response to outbreaks. However, for such fluids, data are scarce for disinfectant efficacy. This information is essential [...]

Ebola virus (EboV) is a highly pathogenic enveloped virus that causes outbreaks of zoonotic infection in Africa. The clinical symptoms are manifestations of the massive production of pro-inflammatory cytokines in response to infection (1) and in many outbreaks, mortality exceeds 75%. The unpredictable onset, ease of transmission, rapid progression of disease, high mortality and lack of effective vaccine or therapy have created a high level of public concern about EboV (2). Here we report the identification of a novel benzylpiperazine adamantane diamide-derived compound that inhibits EboV infection. Using mutant cell lines and informative derivatives of the lead compound, we show that the target of the inhibitor is the endosomal membrane protein Niemann-Pick C1 (NPC1). We find that NPC1 is essential for infection, that it binds to the virus glycoprotein (GP), and that antiviral compounds interfere with GP binding to NPC1. Combined with the results of previous studies of GP structure and function, our findings support a model of EboV infection in which cleavage of the GP1 subunit by endosomal cathepsin proteases removes heavily glycosylated domains to expose the amino-terminal domain (3-7), which is a ligand for NPC1 and regulates membrane fusion by the GP2 subunit (8). Thus, NPC1 is essential for EboV entry and a target for antiviral therapy., To identify chemical probes that target EboV host factors, we screened a library of small molecules and identified a novel benzylpiperazine adamantane diamide, 3.0, that inhibits infection of Vero cells [...]

Orthopoxviruses include the prototypical vaccinia virus, the emerging infectious agent monkeypox virus, and the potential biothreat variola virus (the causative agent of smallpox). There is currently no FDA-approved drug for humans infected with orthopoxviruses. We screened a diversity-oriented synthesis library for new scaffolds with activity against vaccinia virus. This screen identified a nonnucleoside analog that blocked postreplicative intermediate and late gene expression. Viral genome replication was unaffected, and inhibition could be elicited late in infection and persisted upon drug removal. Sequencing of drug-resistant viruses revealed mutations predicted to be on the periphery of the highly conserved viral RNA polymerase large subunit. Consistent with this, the compound had broad-spectrum activity against orthopoxviruses in vitro. These findings indicate that novel chemical synthesis approaches are a potential source for new infectious disease therapeutics and identify a potentially promising candidate for development to treat orthopoxvirus-infected individuals. [ABSTRACT FROM AUTHOR]

Teredinibacter turnerae is a cultivable cellulolytic Gammaproteobacterium (Cellvibrionaceae) that commonly occurs as an intracellular endosymbiont in the gills of wood-eating bivalves of the family Teredinidae (shipworms). The genome of T. turnerae encodes a broad range of enzymes that deconstruct cellulose, hemicellulose, and pectin and contribute to wood (lignocellulose) digestion in the shipworm gut. However, the mechanisms by which T. turnerae secretes lignocellulolytic enzymes are incompletely understood. Here, we show that T. turnerae cultures grown on carboxymethyl cellulose (CMC) produce membrane vesicles (MVs) that include a variety of proteins identified by LC-MS/MS as carbohydrate-active enzymes (CAZymes) with predicted activities against cellulose, hemicellulose, and pectin. Reducing sugar assays and zymography confirm that these MVs exhibit cellulolytic activity, as evidenced by the hydrolysis of CMC. Additionally, these MVs were enriched with TonB -dependent receptors, which are essential to carbohydrate and iron acquisition by free-living bacteria. These observations indicate a potential role for MVs in lignocellulose utilization by T. turnerae in the free-living state, suggest possible mechanisms for host-symbiont interaction, and may be informative for commercial applications such as enzyme production and lignocellulosic biomass conversion., Competing Interests: Conflict of interest statement The authors report no conflict of interest. The funders had no role in study design, data collection, interpretation, or the decision to submit the work for publication.

We present the complete genome sequences of two strains of Teredinibacter turnerae , SR01903 and SR02026, shipworm endosymbionts isolated from the gills of Lyrodus pedicellatus and Teredo bartschi , respectively, and derived from Oxford Nanopore sequencing. These sequences will aid in the comparative genomics of shipworm endosymbionts and understanding of host-symbiont selection.

We present the complete closed circular genome sequence derived from Oxford Nanopore sequencing of the shipworm endosymbiont Teredinibacter turnerae T7902 (DSM 15152, ATCC 39867), originally isolated from the shipworm Lyrodus pedicellatus (1). This sequence will aid in the comparative genomics of shipworm endosymbionts and the understanding of host-symbiont evolution.