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Biology subjects

Ba, M.

Publications and source records attributed to Ba, M..

2 recordsLinked to original sources

Omnicrobe, an open-access database of microbial habitats and phenotypes using a comprehensive text mining and data fusion approach

The dramatic increase in the amount of microbe descriptions in databases, reports and papers presents a two-fold challenge for accessing the information: integration of heterogeneous data in a standard ontology-based representation and normalization of the textual descriptions by semantic analysis. Recent text mining methods offer powerful ways to extract textual information and generate ontology-based representation. This paper describes the design of the Omnicrobe application that gathers comprehensive information on habitats, phenotypes and usages of microbes from scientific sources of high interest to the microbiology community. The Omnicrobe database contains around 1 million descriptions of microbe properties that are created by analyzing and combining six information sources of various kinds, i.e. biological resource catalogues, sequence database and scientific literature. The microbe properties are indexed by the Ontobiotope ontology and their taxa are indexed by an extended version of the taxonomy maintained by the National Center for Biotechnology Information. The Omnicrobe application covers all domains of microbiology. It provides an easy-to-use support in the resolution of scientific questions related to the habitats, phenotypes and uses of microbes through simple and complex ontology-based queries. We illustrate the potential of Omnicrobe with a use case from the food innovation domain.

bioinformatics↗

Discovery of SARS-CoV-2 papain-like protease inhibitors through a combination of high-throughput screening and FlipGFP-based reporter assay

The papain-like protease (PLpro) of SARS-CoV-2 is a validated antiviral drug target. PLpro is involved in the cleavage of viral polyproteins and antagonizing host innate immune response through its deubiquitinating and deISG15ylating activities, rendering it a high profile antiviral drug target. Through a FRET-based high-throughput screening, several hits were identified as PLpro inhibitors with IC50 values at the single-digit micromolar range. Subsequent lead optimization led to potent inhibitors with IC50 values ranging from 0.56 to 0.90 {micro}M. To help prioritize lead compounds for the cellular antiviral assay against SARS-CoV-2, we developed the cell-based FlipGFP assay that is suitable for quantifying the intracellular enzymatic inhibition potency of PLpro inhibitors in the BSL-2 setting. Two compounds selected from the FlipGFP-PLpro assay, Jun9-53-2 and Jun9-72-2, inhibited SARS-CoV-2 replication in Caco-2 hACE2 cells with EC50 values of 8.89 and 8.32 {micro}M, respectively, which were 3-fold more potent than GRL0617 (EC50 = 25.1 {micro}M). The X-ray crystal structures of PLpro in complex with GRL0617 showed that binding of GRL0617 to SARS-CoV-2 induced a conformational change in the BL2 loop to the more closed conformation. Overall, the PLpro inhibitors identified in this study represent promising starting points for further development as SARS-CoV-2 antivirals, and FlipGFP-PLpro assay might be a suitable surrogate for screening PLpro inhibitors in the BSL-2 setting.

pharmacology and toxicology↗