Corpus overview


MeSH Disease

Human Phenotype


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    Next-generation diagnostics: virus capture facilitates a sensitive viral diagnosis for epizootic and zoonotic pathogens including SARS-CoV-2

    Authors: Claudia Wylezich; Sten Calvelage; Kore Schlottau; Ute Ziegler; Anne Pohlmann; Dirk Hoeper; Martin Beer

    doi:10.1101/2020.06.30.181446 Date: 2020-07-01 Source: bioRxiv

    BackgroundThe detection of pathogens in clinical and environmental samples using high-throughput sequencing (HTS) is often hampered by large amounts of background information, which is especially true for viruses with small genomes. Enormous sequencing depth can be necessary to compile sufficient information for identification of a certain pathogen. Generic HTS combining with in-solution capture enrichment can markedly increase the sensitivity SERO for virus detection in complex diagnostic samples. MethodsA virus panel based on the principle of biotinylated RNA-baits was developed for specific capture enrichment of epizootic and zoonotic viruses (VirBaits). The VirBaits set was supplemented by a SARS-CoV-2 predesigned bait set for testing recent SARS-CoV-2 positive samples. Libraries generated from complex samples were sequenced via generic HTS and afterwards enriched with the VirBaits set. For validation, an internal proficiency test for emerging epizootic and zoonotic viruses ( African swine fever MESHD fever HP virus, Ebolavirus, Marburgvirus, Nipah henipavirus, Rift Valley fever MESHD fever HP virus) was conducted. ResultsThe VirBaits set consists of 177,471 RNA-baits (80-mer) based on about 18,800 complete viral genomes targeting 35 epizootic and zoonotic viruses. In all tested samples, viruses with both DNA and RNA genomes were clearly enriched ranging from about 10-fold to 10,000-fold for viruses including distantly related viruses with at least 72% overall identity to viruses represented in the bait set. Viruses showing a lower overall identity (38% and 46%) to them were not enriched but could nonetheless be detected based on capturing conserved genome regions. The internal proficiency test supports the improved virus detection using the combination of HTS plus targeted enrichment but also point to the risk of carryover between samples. ConclusionsThe VirBaits approach showed a high diagnostic performance SERO, also for distantly related viruses. The bait set is modular and expandable according to the favored diagnostics, health sector or research question. The risk of carryover needs to be taken into consideration. The application of the RNA-baits principle turned out to be user-friendly, and even non-experts (without sophisticated bioinformatics skills) can easily use the VirBait workflow. The rapid extension of the established VirBaits set adapted to actual outbreak events is possible without any problems as shown for SARS-CoV-2.

    In search for the hotspots of Disease MESHD X: A biogeographic approach to mapping the predictive risk of WHO s Blueprint Priority Diseases MESHD

    Authors: Soushieta Jagadesh; Marine Combe; Mathieu Nacher; Rodolphe Ellie Gozlan

    doi:10.1101/2020.03.27.20044156 Date: 2020-03-30 Source: medRxiv

    Anthropization of natural habitats including climate change along with overpopulation and global travel TRANS have been contributing to emerging infectious diseases MESHD outbreaks. The recent COVID-19 outbreak in Wuhan, highlights such threats to human health, social stability and global trade and economy. We used species distribution modelling and environmental data from satellite imagery to model Blueprint Priority Diseases MESHD occurrences. We constructed classical regression and Support Vector Machine models based on environmental predictor variables such as landscape, tree cover loss, climatic covariates. Models were evaluated and a weighed mean was used to map the predictive risk of disease MESHD emergence. We mapped the predictive risk for filovirus, Nipah, Rift Valley Fever MESHD Fever HP and coronavirus diseases MESHD. Elevation, tree cover loss and climatic covariates were found to significant factors influencing disease MESHD emergence. We also showed the relevance of disease MESHD biogeography and in the identification potential hotspots for Disease MESHD X in regions in Uganda and China.

    Novel ionophores active against La Crosse virus identified through rapid antiviral screening

    Authors: Zachary J Sandler; Michelle N Vu; Vineet D. Menachery; Bryan C. Mounce

    doi:10.1101/2020.01.21.914929 Date: 2020-01-23 Source: bioRxiv

    Bunyaviruses are significant human pathogens, causing diseases MESHD ranging from hemorrhagic fevers MESHD fevers HP to encephalitis MESHD encephalitis HP. Among these viruses, La Crosse virus (LACV), a member of the California serogroup, circulates in the eastern and midwestern United States. While LACV infection is often asymptomatic MESHD asymptomatic TRANS, dozens of cases of encephalitis MESHD encephalitis HP are reported yearly. Unfortunately, no antivirals have been approved to treat LACV infection MESHD. Here, we developed a method to rapidly test SERO potential antivirals against LACV infection MESHD. From this screen, we identified several potential antiviral molecules, including known antivirals. Additionally, we identified many novel antivirals that exhibited antiviral activity without affecting cellular viability. Valinomycin, a potassium ionophore, was among our top targets. We found that valinomycin exhibited potent anti-LACV activity in multiple cell types in a dose-dependent manner. Valinomycin did not affect particle stability or infectivity, suggesting that it may preclude virus replication by altering cellular potassium ions, a known determinant of LACV entry. We extended these results to other ionophores and found that the antiviral activity of valinomycin extended to other viral families including bunyaviruses ( Rift Valley fever MESHD fever HP virus, Keystone virus), enteroviruses (Coxsackievirus, rhinovirus), flavirivuses (Zika), and coronaviruses (229E and MERS-CoV). In all viral infections MESHD, we observed significant reductions in virus titer in valinomycin-treated cells. In sum, we demonstrate the importance of potassium ions to virus infection MESHD, suggesting a potential therapeutic target to disrupt virus replication. ImportanceNo antivirals are approved for the treatment of bunyavirus infection MESHD. The ability to rapidly screen compounds and identify novel antivirals is one means to accelerate drug discovery for viruses with no approved treatments. We used this approach to screen hundreds of compounds against La Crosse virus, an emerging bunyavirus that causes significant disease MESHD, including encephalitis MESHD encephalitis HP. We identified several known and previously unidentified antivirals. We focused on a potassium ionophore, valinomycin, due to its promising in vitro antiviral activity. We demonstrate that valinomycin, as well as a selection of other ionophores, exhibits activity against La Crosse virus as well as several other distantly related bunyaviruses. We finally observe that valinomycin has activity against a wide array of human viral pathogens, suggesting that disrupting potassium ion homeostasis with valinomycin may be a potent host pathway to target to quell virus infection MESHD.

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MeSH Disease
Human Phenotype

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