Decorin as a possible strategy for the amelioration of COVID-19

Abstract

Coronavirus pandemic has emerged as an extraordinary healthcare crisis in modern times. The SARS-CoV-2 novel coronavirus has high transmission rate, is more aggressive and virulent in comparison to previously known coronaviruses. It primarily attacks the respiratory system by inducing cytokine storm that causes systemic inflammation and pulmonary fibrosis. Decorin is a pluripotent molecule belonging to a leucine rich proteoglycan group that exerts critical role in extracellular matrix (ECM) assembly and regulates cell growth, adhesion, proliferation, inflammation, and fibrogenesis. Interestingly, decorin has potent anti-inflammatory, cytokine inhibitory, and anti-fibrillogenesis effects which make it a potential drug candidate against the COVID-19 related complications especially in the context of lung fibrosis. Herein, we postulate that owing to its distinctive pharmacological actions and immunomodulatory effect, decorin can be a promising preclinical therapeutic agent for the therapy of COVID-19.

Keywords: COVID-19; Decorin; Fibrosis; Immunomodulation; Lung injury.

Fig. 1

TGF-β triggers the downstream activation of important signaling events of rat sarcoma (RAS) which are involved in the cooperation with the TGF-β/Smad family including the RAS-activated factor (RAF)/mitogen activated protein kinase (MAPK), extracellular regulated kinase (ERK) kinase (MEK)/ERK pathway (RAS-RAF-MEK-ERK signaling). Moreover, TGF-β phosphorylation activates the Smad2, Smad3, and Smad4 signaling cascade involved in the fibrotic process. SARS-CoV-2 stimulates the excess activation of TGF-β which in turn triggers the process of fibrosis. Decorin can effectively inhibit TGF-β, thereby sequestering the whole signaling pathway resulting in the reduction of fibrotic scar. The figure was created with BioRender.com.

Fig. 2

Role of soluble form of decorin in comparison with matrix-bound decorin in healing and fibrosis. Soluble decorin works as a signaling molecule of the insulin like growth factor I receptor (IGF-IR), hence, shielding epithelial cells against apoptosis or inducing the production of fibrillin-1 in fibroblasts. Furthermore, decorin is capable of neutralizing the activity of TGF-β directly or indirectly through the modulation of fibrillin-1. In the event of fibrosis, most of the decorin is bound to cellular matrix components, mainly to collagen type I, as a part of fibrotic scar and consequently is incapable to act as a signaling molecule. However, matrix-bound decorin is still capable to sequester TGF-β in the matrix, thus, withdrawing the cytokine from its cell membrane receptors. The figure was created with BioRender.com.