tetano
Editor, Senior Moderator
Pharmacol Rep
. 2021 Apr 21.
doi: 10.1007/s43440-021-00255-x. Online ahead of print.
Role of pirfenidone in TGF-? pathways and other inflammatory pathways in acute respiratory syndrome coronavirus 2 (SARS-Cov-2) infection: a theoretical perspective
Seyed Hootan Hamidi[SUP] 1 [/SUP], Sandhya Kadamboor Veethil[SUP] 2 [/SUP], Seyedeh Harir Hamidi[SUP] 3 [/SUP]
Affiliations
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-?) is a key factor that is released during SARS-CoV-2 infection. TGF-?, 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-?) 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.
Keywords: COVID-19 therapy; Pathology of COVID-19; Pirfenidone mechanism of action; SARS-CoV-2 mechanism; TGF-? signaling.
. 2021 Apr 21.
doi: 10.1007/s43440-021-00255-x. Online ahead of print.
Role of pirfenidone in TGF-? pathways and other inflammatory pathways in acute respiratory syndrome coronavirus 2 (SARS-Cov-2) infection: a theoretical perspective
Seyed Hootan Hamidi[SUP] 1 [/SUP], Sandhya Kadamboor Veethil[SUP] 2 [/SUP], Seyedeh Harir Hamidi[SUP] 3 [/SUP]
Affiliations
- PMID: 33880743
- DOI: 10.1007/s43440-021-00255-x
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-?) is a key factor that is released during SARS-CoV-2 infection. TGF-?, 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-?) 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.
Keywords: COVID-19 therapy; Pathology of COVID-19; Pirfenidone mechanism of action; SARS-CoV-2 mechanism; TGF-? signaling.