About: Morphological Cell Profiling of SARS-CoV-2 Infection Identifies Drug Repurposing Candidates for COVID-19

Facets (new session)
Description
Metadata
Settings
- owl:sameAs
- Inference Rule:

About: Morphological Cell Profiling of SARS-CoV-2 Infection Identifies Drug Repurposing Candidates for COVID-19 Goto Sponge NotDistinct Permalink

An Entity of Type : schema:ScholarlyArticle, within Data Space : covidontheweb.inria.fr associated with source document(s)

Attributes	Values
type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
title	Morphological Cell Profiling of SARS-CoV-2 Infection Identifies Drug Repurposing Candidates for COVID-19
Creator	Spence, Jason Kotton, Darrell Sexton, Jonathan Wobus, Christiane Mirabelli, Carmen O'meara, Matthew Alysandratos, Konstantinos Amin, Anya Frum, Tristan Handelman, Samuel Huang, Jessie Kadambi, Namrata Mashour, George Weatherwax, Kevin Wotring, Jesse Zhang, Charles Fursmidt, Mccarty, Sean O'meara, Teresa Pretto,
source	BioRxiv; Medline; PMC; WHO
abstract	The global spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the associated disease COVID-19, requires therapeutic interventions that can be rapidly translated to clinical care. Unfortunately, traditional drug discovery methods have a >90% failure rate and can take 10–15 years from target identification to clinical use. In contrast, drug repurposing can significantly accelerate translation. We developed a quantitative high-throughput screen to identify efficacious single agents and combination therapies against SARS-CoV-2. Quantitative high-content morphological profiling was coupled with an AI-based machine learning strategy to classify features of cells for infection and stress. This assay detected multiple antiviral mechanisms of action (MOA), including inhibition of viral entry, propagation, and modulation of host cellular responses. From a library of 1,425 FDA-approved compounds and clinical candidates, we identified 16 dose-responsive compounds with antiviral effects. In particular, we discovered that lactoferrin is an effective inhibitor of SARS-CoV-2 infection with an IC(50) of 308 nM and that it potentiates the efficacy of both remdesivir and hydroxychloroquine. Lactoferrin also stimulates an antiviral host cell response and retains inhibitory activity in iPSC-derived alveolar epithelial cells, a model for the primary site of infection. Given its safety profile in humans, these data suggest that lactoferrin is a readily translatable therapeutic adjunct for COVID-19. Additionally, several commonly prescribed drugs were found to exacerbate viral infection and warrant clinical investigation. We conclude that morphological profiling for drug repurposing is an effective strategy for the selection and optimization of drugs and drug combinations as viable therapeutic options for COVID-19 pandemic and other emerging infectious diseases.
has issue date	2020-06-10(xsd:dateTime)
bibo:doi	10.1101/2020.05.27.117184
bibo:pmid	32577649
has license	cc-by-nc-nd
sha1sum (hex)	34f81ecc015da1646bef3d5c5d6c32a1ae7a983e
schema:url	https://doi.org/10.1101/2020.05.27.117184
resource representing a document's title	Morphological Cell Profiling of SARS-CoV-2 Infection Identifies Drug Repurposing Candidates for COVID-19
has PubMed Central identifier	PMC7302203
has PubMed identifier	32577649
schema:publication	bioRxiv
resource representing a document's body	covid:34f81ecc015da1646bef3d5c5d6c32a1ae7a983e#body_text
is schema:about of	named entity 'COVID-19' named entity 'Infection' named entity 'COVID' named entity 'Morphological' named entity 'alveolar epithelium' named entity 'IFITM3' named entity 'SARS-CoV-1' named entity 'S1RA' named entity 'phase II clinical trials' named entity 'SARS-CoV-2' named entity 'thioguanine' named entity 'gastrointestinal' named entity 'lactoferrin' named entity 'SARS-CoV-2' named entity 'antiviral activity' named entity 'hERG' named entity 'SARS-CoV-1' named entity 'SARS-CoV-2' named entity 'ritonavir' named entity 'FDA' named entity 'carbidopa' named entity 'entecavir' named entity 'interferon-stimulated genes' named entity 'alveolar' named entity 'epithelial cells' named entity 'tocilizumab' named entity 'lomitapide' named entity 'trametinib' named entity 'antiviral activity' named entity 'Viperin' named entity 'cell lines' named entity 'IL-6' named entity 'nausea and vomiting' named entity 'viral replication' named entity 'viral entry' named entity 'dietary supplements' named entity 'binimetinib' named entity 'infection' named entity 'S1RA' named entity 'gastrointestinal symptoms' named entity 'Gastrointestinal symptoms' named entity 'IFNβ' named entity 'SARS' named entity 'protein' named entity 'viral entry' named entity 'natural killer cell' named entity 'bosutinib' named entity 'bronchial' named entity 'MOIs' named entity 'infection' named entity 'lactoferrin' named entity 'pathogenesis' named entity 'machine learning' named entity '24 hrs' named entity 'lactoferrin' named entity 'dopamine receptor D2' named entity 'verapamil' named entity 'neutrophil' named entity 'cardiotoxic' named entity 'hydroxychloroquine' named entity 'potency' named entity 'metoclopramide'

Faceted Search & Find service v1.13.91 as of Mar 24 2020

Alternative Linked Data Documents: Sponger | ODE Content Formats:

RDF

ODATA

Microdata

About

OpenLink Virtuoso version 07.20.3229 as of Jul 10 2020, on Linux (x86_64-pc-linux-gnu), Single-Server Edition (94 GB total memory)
Data on this page belongs to its respective rights holders.
Virtuoso Faceted Browser Copyright © 2009-2025 OpenLink Software