Year: 2022
Type: preprint
Abstract: SUMMARY The Omicron variant has become dominant in the U.S. and around the world. This variant is found to be 2-fold more infectious than the Delta variant, posing a significant threat of severe cases and death. We and others have recently reported that the N-terminus domain (NTD) of the SARS-CoV-2 of various variants is responsible for inducing cytokine release in human PBMCs. Here, we demonstrate that the NTD of the Omicron variant remains highly effective at inducing cytokine release in human PBMCs. Furthermore, we show that Ponatinib and a novel compound, Olverembatinib, are potent Omicron NTD-mediated cytokine release inhibitors. Target profiling revealed that Olverembatinib blocks most of the previously identified kinases responsible for cytokine release. Together, we propose that Ponatinib and Olverembatinib may represent an attractive therapeutic option for treating moderate to severe COVID-19 cases. HIGHLIGHTS The N-terminus domain (NTD) of the SARS-CoV-2 Omicron variant strongly induces multiple inflammatory molecules in PBMCs, unaffected by the mutations observed in the NTD. The cytokine release mediated by the Omicron variant is comparable to the Delta variant. Olverembatinib, a clinical-stage multi-kinase inhibitor, potently inhibits Omicron NTD-mediated cytokine release. Olverembatinib could relieve severe symptoms associated with COVID-19 Omicron and Delta variants.
Institutions: Fred Hutch Cancer Center, University of Washington
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W4211050499