Is GSK3β a molecular target of chloroquine treatment against COVID-19?

Abstract

The recent clinical trial reports pertaining to the efficacy of chloroquine and hydroxychloroquine against COVID-19 albeit yet to be validated with larger clinical trials, have sparked much interest globally to evaluate whether this anti-malarial drug can be repurposed for the treatment of COVID-19. In addition to its anti-viral activity, the anti-inflammatory activity of chloroquine may also contribute to its efficacy. Based on our data obtained from an animal infection model of melioidosis (a disease caused by the bacteria Burkholderia pseudomallei), treatment with chloroquine can result in the phosphorylation and consequent inhibition of glycogen synthase kinase-3β (GSK3β). This serine/threonine protein kinase is now recognised as a point of convergence for host inflammatory response. In view of this, it is plausible that the mechanism for the anti-inflammatory effect of chloroquine against COVID-19 involves inhibition of host GSK3β.