Targeting Lymphocyte Kv1.3-channels to Suppress Cytokine Storm in Severe COVID-19: Can It Be a Novel Therapeutic Strategy?

Drug Discov Ther. 2020 Jun 25. doi: 10.5582/ddt.2020.03046. Online ahead of print.

Abstract

In the midst of a pandemic, finding effective treatments for coronavirus disease 2019 (COVID-19) is the urgent issue. In "chronic inflammatory diseases", the overexpression of delayed rectifier K+-channels (Kv1.3) in leukocytes is responsible for the overactivation of cellular immunity and the subsequent cytokine storm. In our previous basic studies, drugs including chloroquine and azithromycin strongly suppressed the channel activity and pro-inflammatory cytokine production from lymphocytes. These findings suggest a novel pharmacological mechanism by which chloroquine, with or without azithromycin, is effective for severe cases of COVID-19, in which the overactivation of cellular immunity and the subsequent cytokine storm are responsible for the pathogenesis.

Keywords: COVID-19; Kv1.3-channels; chloroquine; cytokine storm; lymphocyte.