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Exhaustive drug repurposing strategies support the pursuit of new chemical entities for the development of effective COVID-19 interventions

ABSTRACT: Exhaustive drug repurposing strategies support the pursuit of new chemical entities for the development of effective COVID-19 interventions

PROVIDER: PRJNA706017 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR13833624_1.fastq.gz	Fastqsanger.gz
	SRR13833624_2.fastq.gz	Fastqsanger.gz
	SRR13833625_1.fastq.gz	Fastqsanger.gz
	SRR13833625_2.fastq.gz	Fastqsanger.gz
	SRR13833626_1.fastq.gz	Fastqsanger.gz

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Exhaustive drug repurposing strategies support the pursuit of new chemical entities for the development of effective COVID-19 interventions

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Drug repurposing screens identify chemical entities for the development of COVID-19 interventions.

Project description:The ongoing pandemic caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), necessitates strategies to identify prophylactic and therapeutic drug candidates for rapid clinical deployment. Here, we describe a screening pipeline for the discovery of efficacious SARS-CoV-2 inhibitors. We screen a best-in-class drug repurposing library, ReFRAME, against two high-throughput, high-content imaging infection assays: one using HeLa cells expressing SARS-CoV-2 receptor ACE2 and the other using lung epithelial Calu-3 cells. From nearly 12,000 compounds, we identify 49 (in HeLa-ACE2) and 41 (in Calu-3) compounds capable of selectively inhibiting SARS-CoV-2 replication. Notably, most screen hits are cell-line specific, likely due to different virus entry mechanisms or host cell-specific sensitivities to modulators. Among these promising hits, the antivirals nelfinavir and the parent of prodrug MK-4482 possess desirable in vitro activity, pharmacokinetic and human safety profiles, and both reduce SARS-CoV-2 replication in an orthogonal human differentiated primary cell model. Furthermore, MK-4482 effectively blocks SARS-CoV-2 infection in a hamster model. Overall, we identify direct-acting antivirals as the most promising compounds for drug repurposing, additional compounds that may have value in combination therapies, and tool compounds for identification of viral host cell targets.

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SHOME-BIO (SHOtgun MEtagenomic analysis of BIOlogical entities): from reads to pathogens. A specific and exhaustive pipeline for handling metagenomic shotgun sequencing data.

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Project description:SHOME-BIO (SHOtgun MEtagenomic analysis of BIOlogical entities): from reads to pathogens. A specific and exhaustive pipeline for handling metagenomic shotgun sequencing data.

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HOME-BIO (sHOtgun MEtagenomic analysis of BIOlogical entities): from reads to pathogens. A specific and exhaustive pipeline for handling metagenomic shotgun sequencing data.

Project description:Next-Generation-Sequencing (NGS) technologies have led to important improvement in the detection of new or unrecognized infective agents, related to infectious diseases. In this context, NGS high-throughput technology can be used to achieve a comprehensive and unbiased sequencing of the nucleic acids present in a clinical sample (i.e. tissues). Metagenomic shotgun sequencing has emerged as powerful high-throughput approaches to analyze and survey microbial composition in the field of infectious diseases. By directly sequencing millions of nucleic acid molecules in a sample and matching the sequences to those available in databases, pathogens of an infectious disease can be inferred. Despite the large amount of metagenomic shotgun data produced, there is a lack of a comprehensive and easy-use pipeline for data analysis that avoid annoying and complicated bioinformatics steps. Here we present HOME-BIO, a modular and exhaustive pipeline for analysis of biological entity estimation, specific designed for shotgun sequenced clinical samples. HOME-BIO analysis provides comprehensive taxonomy classification by querying different source database and carry out main steps in metagenomic investigation. HOME-BIO is a powerful tool in the hand of biologist without computational experience, which are focused on metagenomic analysis. Its easy-to-use intrinsic characteristic allows users to simply import raw sequenced reads file and obtain taxonomy profile of their samples.

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