Role of pirfenidone in TGF-β pathways and other inflammatory pathways in acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection: a theoretical perspective

Abstract

Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes pulmonary injury or multiple-organ injury by various pathological pathways. Transforming growth factor-beta (TGF-β) is a key factor that is released during SARS-CoV-2 infection. TGF-β, by internalization of the epithelial sodium channel (ENaC), suppresses the anti-oxidant system, downregulates the cystic fibrosis transmembrane conductance regulator (CFTR), and activates the plasminogen activator inhibitor 1 (PAI-1) and nuclear factor-kappa-light-chain-enhancer of activated B cells (NF-kB). These changes cause inflammation and lung injury along with coagulopathy. Moreover, reactive oxygen species play a significant role in lung injury, which levels up during SARS-CoV-2 infection. Drug Suggestion Pirfenidone is an anti-fibrotic drug with an anti-oxidant activity that can prevent lung injury during SARS-CoV-2 infection by blocking the maturation process of transforming growth factor-beta (TGF-β) and enhancing the protective role of peroxisome proliferator-activated receptors (PPARs). Pirfenidone is a safe drug for patients with hypertension or diabetes and its side effect tolerated well. Conclusion The drug as a theoretical perspective may be an effective and safe choice for suppressing the inflammatory response during COVID-19. The recommendation would be a combination of pirfenidone and N -acetylcysteine to achieve maximum benefit during SARS-CoV-2 treatment.

Comparison of pirfenidone and corticosteroid treatments at the COVID‐19 pneumonia with the guide of artificial intelligence supported thoracic computed tomography

“…Pirfenidone is a safe drug for patients with hypertension or diabetes and its side effects are well tolerated. 35 …”

Circadian rhythm disruption in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Implications for the post-acute sequelae of COVID-19

“…To promote viral proliferation, SARS-CoV2 reduces the ability of infected cells to undergo apoptosis by altering TGFB signaling through a variety of direct and indirect mechanisms ( Mirzaei and Faghihloo, 2018 ; Hamidi and KadamboorVeethil, 2021 ). SARS-CoV nucleocapsid protein alters TGFB signaling pathways by interacting directly with SMAD3-4 proteins ( Zhao et al., 2008 ).…”

Aryl Hydrocarbon Receptor Mechanisms Affecting Chronic Kidney Disease

“…The exact mechanisms of action of pirfenidone are not fully characterized. Recent studies suggest the molecule may be a ligand for peroxisome proliferator-activated receptors (e.g., PPAR-α, PPAR-γ) ( Hamidi et al, 2021 ), which appears to inhibit transforming growth factor (TGF)-β1-induced collagen I production ( Cui et al, 2020 ). Pirfenidone may also suppress other profibrotic and pro-inflammatory mediators, including fibroblast growth factor (FGF), platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF) ( Chaudhary et al, 2007 ), interleukin-1β (IL-1β) and tumor necrosis factor (TNF) ( Evani et al, 2020 ).…”