Cannabinoid Receptor Type 2: A Possible Target in SARS-CoV-2 (CoV-19) Infection?

Abstract

In late December 2019, a novel coronavirus (SARS-CoV-2 or CoV-19) appeared in Wuhan, China, causing a global pandemic. SARS-CoV-2 causes mild to severe respiratory tract inflammation, often developing into lung fibrosis with thrombosis in pulmonary small vessels and causing even death. COronaVIrus Disease (COVID-19) patients manifest exacerbated inflammatory and immune responses, cytokine storm, prevalence of pro-inflammatory M1 macrophages and increased levels of resident and circulating immune cells. Men show higher susceptibility to SARS-CoV-2 infection than women, likely due to estrogens production. The protective role of estrogens, as well as an immune-suppressive activity that limits the excessive inflammation, can be mediated by cannabinoid receptor type 2 (CB2). The role of this receptor in modulating inflammation and immune response is well documented in fact in several settings. The stimulation of CB2 receptors is known to limit the release of pro-inflammatory cytokines, shift the macrophage phenotype towards the anti-inflammatory M2 type and enhance the immune-modulating properties of mesenchymal stromal cells. For these reasons, we hypothesize that CB2 receptor can be a therapeutic target in COVID-19 pandemic emergency.

Keywords: COVID-19; SARS-CoV-2; cannabinoid receptor type 2; endocannabinoids system; immune response; inflammation; molecular target; therapeutic strategies.

Figure 1

Inflammatory response in lung after coronavirus (SARS-CoV-2) infection. Lung susceptibility to SARS-CoV-2 infection depends on viral spike proteins specificity for angiotensin-converting enzyme 2 (ACE2) receptors on alveolar epithelial cells. This interaction leads to hyperinflammation sustained by cytokine storm, increase of pro-inflammatory M1 macrophages and T-helper cells, all associated in a vicious circle in which each event enhances the alteration of the other ones. The selective stimulation of Cannabinoid Receptor type 2 (CB2) receptors on macrophages, T-helper cells and mesenchymal stromal cells (MSCs) could be proposed to contain the inflammatory state in COVID-19 patients.