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

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

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 proposed anti‐cytokine effects and as an inhibitor of ho...

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Main Authors: Justin Stebbing, Venkatesh Krishnan, Stephanie de Bono, Silvia Ottaviani, Giacomo Casalini, Peter J Richardson, Vanessa Monteil, Volker M Lauschke, Ali Mirazimi, Sonia Youhanna, Yee‐Joo Tan, Fausto Baldanti, Antonella Sarasini, Jorge A Ross Terres, Brian J Nickoloff, Richard E Higgs, Guilherme Rocha, Nicole L Byers, Douglas E Schlichting, Ajay Nirula, Anabela Cardoso, Mario Corbellino, the Sacco Baricitinib Study Group
Format: Article
Language:English
Published: Springer Nature 2020-06-01
Series:EMBO Molecular Medicine
Subjects:
anti‐cytokine
anti‐viral
baricitinib
case series
COVID‐19
Online Access:https://doi.org/10.15252/emmm.202012697
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Summary: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 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 support its assessment in randomized trials in hospitalized COVID‐19 patients.
ISSN:1757-4676
1757-4684

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