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Systematic review and meta-analysis identifies potential host therapeutic targets in COVID-19. (preprint)
medrxiv; 2020.
Preprint
in English
| medRxiv | ID: ppzbmed-10.1101.2020.08.27.20182238
ABSTRACT
An increasing body of literature describes the role of host factors in COVID-19 pathogenesis. There is a need to combine diverse, multi-omic data in order to evaluate and substantiate the most robust evidence and inform development of future therapies. We conducted a systematic review of experiments identifying host factors involved in human betacoronavirus infection (SARS-CoV-2, SARS-CoV, MERS-CoV, seasonal coronaviruses). Gene lists from these diverse sources were integrated using Meta-Analysis by Information Content (MAIC). This previously described algorithm uses data-driven gene list weightings to produce a comprehensive ranked list of implicated host genes. 5,418 genes implicated in human betacoronavirus infection were identified from 32 datasets. The top ranked gene was *PPIA*, encoding cyclophilin A. Pharmacological inhibition with cyclosporine in vitro exerts antiviral activity against several coronaviruses including SARS-CoV. Other highly-ranked genes included proposed prognostic factors (*CXCL10*, *CD4*, *CD3E*) and investigational therapeutic targets (*IL1A*) for COVID-19, but also previously overlooked genes with potential as therapeutic targets. Gene rankings also inform the interpretation of COVID-19 GWAS results, implicating *FYCO1* over other nearby genes in a disease-associated locus on chromosome 3. Pathways enriched in gene rankings included T-cell receptor signalling, protein processing, and viral infections. We identified limited overlap of our gene list with host genes implicated in ARDS (innate immune and inflammation genes) and Influenza A virus infection (RNA-binding and ribosome-associated genes). We will continue to update this dynamic ranked list of host genes as the field develops, as a resource to inform and prioritise future studies. Updated results are available at https//baillielab.net/maic/covid19.
Full text:
Available
Collection:
Preprints
Database:
medRxiv
Main subject:
Tumor Virus Infections
/
Virus Diseases
/
Severe Acute Respiratory Syndrome
/
COVID-19
/
Infections
/
Inflammation
Language:
English
Year:
2020
Document Type:
Preprint
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