20
IRUS Total
Downloads

Mechanism of baricitinib supports artificial intelligence-predicted testing in COVID-19 patients

File Description SizeFormat 
emmm.202012697.pdfPublished version1.28 MBAdobe PDFView/Open
Title: Mechanism of baricitinib supports artificial intelligence-predicted testing in COVID-19 patients
Authors: Stebbing, J
Krishnan, V
De Bono, S
Ottaviani, S
Casalini, G
Richardson, PJ
Monteil, V
Lauschke, VM
Mirazimi, A
Youhanna, S
Tan, Y-J
Baldanti, F
Sarasini, A
Terres, JAR
Nickoloff, BJ
Higgs, RE
Rocha, G
Byers, NL
Schlichting, DE
Nirula, A
Cardoso, A
Corbellino, M
Sacco Baricitinib Study Group
Item Type: Journal Article
Abstract: Baricitinib, is an oral Janus kinase (JAK)1/JAK2 inhibitor approved for the treatment of rheumatoid arthritis (RA) that was independently predicted, using artificial intelligence (AI)-algorithms, to be useful for COVID-19 infection via a proposed anti-cytokine effects and as an inhibitor of host cell viral propagation. We evaluated the in vitro pharmacology of baricitinib across relevant leukocyte subpopulations coupled to its in vivo pharmacokinetics and showed it inhibited signaling of cytokines implicated in COVID-19 infection. We validated the AI-predicted biochemical inhibitory effects of baricitinib on human numb-associated kinase (hNAK) members measuring nanomolar affinities for AAK1, BIKE, and GAK. Inhibition of NAKs led to reduced viral infectivity with baricitinib using human primary liver spheroids. These effects occurred at exposure levels seen clinically. In a case series of patients with bilateral COVID-19 pneumonia, baricitinib treatment was associated with clinical and radiologic recovery, a rapid decline in SARS-CoV-2 viral load, inflammatory markers, and IL-6 levels. Collectively, these data support further evaluation of the anti-cytokine and anti-viral activity of baricitinib and supports its assessment in randomized trials in hospitalized COVID-19 patients.
Issue Date: 7-Aug-2020
Date of Acceptance: 28-May-2020
URI: http://hdl.handle.net/10044/1/80104
DOI: 10.15252/emmm.202012697
ISSN: 1757-4676
Publisher: Wiley
Start Page: 1
End Page: 15
Journal / Book Title: EMBO Molecular Medicine
Volume: 12
Issue: 8
Copyright Statement: © 2020 Eli Lilly and Company. Published under the terms of the CC BY 4.0 license (https://creativecommons.org/licenses/by/4.0/)
Sponsor/Funder: National Institute for Health Research
Funder's Grant Number: NIHR-RP-011-053
Keywords: Science & Technology
Life Sciences & Biomedicine
Medicine, Research & Experimental
Research & Experimental Medicine
anti-cytokine
anti-viral
baricitinib
case series
COVID-19
CLATHRIN
SAFETY
CELLS
ENTRY
Science & Technology
Life Sciences & Biomedicine
Medicine, Research & Experimental
Research & Experimental Medicine
anti-cytokine
anti-viral
baricitinib
case series
COVID-19
CLATHRIN
SAFETY
CELLS
ENTRY
COVID-19
anti-cytokine
anti-viral
baricitinib
case series
Adult
Aged
Antiviral Agents
Artificial Intelligence
Azetidines
Betacoronavirus
COVID-19
Coronavirus Infections
Cytokines
Drug Evaluation, Preclinical
Drug Repositioning
Female
Humans
Intracellular Signaling Peptides and Proteins
Leukocytes
Liver
Male
Middle Aged
Pandemics
Pneumonia, Viral
Protein Kinase Inhibitors
Protein-Serine-Threonine Kinases
SARS-CoV-2
Spheroids, Cellular
Sulfonamides
Sacco Baricitinib Study Group
Liver
Leukocytes
Spheroids, Cellular
Humans
Pneumonia, Viral
Coronavirus Infections
Sulfonamides
Azetidines
Protein-Serine-Threonine Kinases
Intracellular Signaling Peptides and Proteins
Cytokines
Protein Kinase Inhibitors
Antiviral Agents
Drug Evaluation, Preclinical
Artificial Intelligence
Adult
Aged
Middle Aged
Female
Male
Drug Repositioning
Pandemics
Betacoronavirus
COVID-19
SARS-CoV-2
Baricitinib
COVID-19
anti-cytokine
anti-viral
case series
06 Biological Sciences
11 Medical and Health Sciences
Publication Status: Published
Conference Place: England
Article Number: e12697
Online Publication Date: 2020-06-24
Appears in Collections:Department of Surgery and Cancer
Faculty of Medicine
Imperial College London COVID-19



This item is licensed under a Creative Commons License Creative Commons