Work

Machine Learning Identifies Ponatinib as a Potent Inhibitor of SARS-CoV2-induced Cytokine Storm

Year: 2021

Type: preprint

Abstract: Although 15-20% of COVID-19 patients experience hyper-inflammation induced by massive cytokine production, cellular triggers of this process and strategies to target them remain poorly understood. Here, we show that the N-terminal domain (NTD) of the spike protein from the SARS-CoV-2 and emerging variants B1.1.7 and B.1.351 substantially induces multiple inflammatory molecules in human monocytes and PBMCs. Further, we identified several protein kinases, including JAK1, EPHA7, IRAK1, MAPK12, and MAP3K8, as essential downstream mediators of NTD-induced cytokine release. Additionally, we found that the FDA-approved, multi-kinase inhibitor Ponatinib is a potent inhibitor of the NTD-mediated cytokine storm. Taken together, we propose that agents targeting multiple kinases required for the SARS-CoV-2-mediated cytokine storm, such as Ponatinib, may represent an attractive therapeutic option for treating moderate to severe COVID-19.

Source: bioRxiv (Cold Spring Harbor Laboratory)

DOI: 10.1101/2021.04.07.438871

Authors: Marina Chan, Siddharth Vijay, M. Juliana McElrath, Eric C. Holland, Taranjit S Gujral

Institutions: Fred Hutch Cancer Center, University of Washington

Language: English

Topic: SARS-CoV-2 and COVID-19 Research

Subfield: Infectious Diseases

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: green

Funders: Fred Hutchinson Cancer Research Center, Office of Research Infrastructure Programs, National Institutes of Health