TABLE 3.
Innovative and repurposed medications in research for pharmacological treatment of Post-COVID-19 pulmonary fibrosis (Echeverría-Esnal et al., 2021; Kumar et al. 2021; Bazdyrev et al. 2021; Cherrez-Ojeda et al. 2022; Mohammadi et al. 2022; Wu et al. 2020; Zheng et al. 2023).
| Medication | Characteristics |
|---|---|
| Spironolactone | Spironolactone acts through spironolactone-dependent upregulation of the adenosine A2A receptor, which plays an important role in the epithelial-mesenchymal transition process. Spironolactone could modulate the extracellular matrix synthesis through its receptors |
| Azithromycin | The macrolide antibiotic with pleiotropic properties inhibits the proliferation of fibroblasts, collagen synthesis, TGF-β synthesis with the corresponding suppression of pro-fibrotic genes, the PI3K/AKT and JAK/STAT signal pathways which are involved in the fibrotic tissue remodelling |
| Colchicine | An anti-inflammatory drug that inhibits the synthesis of TNF-α, IL-6, monocyte migration and secretion of MMP-9. All of these effects undermine the fibrotic impact of severe COVID-19 |
| Treamid | Treamid is a bis-amide derivative of dicarboxylic acid (BDDA). Treamid causes anti-inflammatory and antifibrotic effects by suppressing the production and deposition of collagen and stimulating endothelial progenitor cell synthesis |
| Deupirfenidone | N-aryl pirfenidone derivate with higher expected efficiency compared with pirfenidone. Inhibits various proinflammatory mediators, such as IL-6, TNF-α and TGF-β. Presumably with better gastrointestinal tolerance |
| Collagen-Polyvinylpyrrolidone | Drug with broad effectiveness for supressing multiple cytokines during cytokine storm in COVID-19; stimulates the suppression of tissue fibrosis via the TGFβ-pathway |
| Bovhyaluronidase Azoximer (Longidase) | Bovhyaluronidase azoximer is a long-acting hyaluronidase with antifibrotic properties due to the disruption of collagen fibre formation through the degradation of glycosaminoglycans by hyaluronidase |
| Genistein | Genistein is a soy isoflavone with a structure similar to that of oestrogen (phytoestrogen). Genistein suppresses the expression of transcription factors (NF-κB) and c-Myc and can contribute to cell cycle arrest by inducing the expression of cell cycle inhibitor proteins |
| Tetrandrine | Tetrandrine is a natural alkaloid, a major active component of the Stephania tetrandra plant. Tetrandrine shows multidirectional action, affecting reactive oxygen species, calcium channels and caspase-dependent pathways, with subsequent antitumour, anti-inflammatory and antiviral activity. Moreover, tetrandrine TET can lower type I and III collagen mRNA and collagen deposition in lungs |
| Anluohuaxian | Anluohuaxian is recommended for the treatment of liver fibrosis in China. Anluo-huaxian is known to suppress the expression of type I and III collagen mRNAs, the tissue inhibitor of matrix metalloprotease-1 (TIMP-1) and TGF-β1 in patients with liver fibrosis |
| Stromal Vascular Fraction (cSVF) | Regenerative medicine based on stromal vascular fraction cells (cSVF) derived from adipose tissue. cSVF is known to help mitigate damage from severe inflammatory disorders, provide immunomodulation and promote repair and regenerative effects |
| IN01 vaccine | Anti-EGF polyclonal neutralising antibodies, thereby preventing the binding of this factor to its receptors, blocking the signalling of pathways related to the growth of tumour growth factor and fibrosis |
| Chitotriosidase Inhibitor OATD-01 | Chitotriosidase (chitinase 1) was shown to enhance TGF-β1-stimulated fibrotic responses |
| PRM-151 | Recombinant form of the serum Amyloid P |
| Pamrevlumab | Monoclonal antibody against CTGF (connective tissue growth factor) |
| GLPG1690 | Autotaxin and lysophosphatidic acid inhibitor |
| Resveratrol | Resveratrol, a natural polyphenol, is known to exert several pharmacological effects on lung injury. The antiviral efficacy of Resveratrol was demonstrated for several viruses, including coronavirus. Resveratrol was shown to mitigate the major pathways involved in the pathogenesis of SARS-CoV-2, including regulation of the renin-angiotensin system (RAS) and expression of angiotensin-converting enzyme 2 (ACE2), stimulation of immune system and downregulation of proinflammatory and profibrotic cytokines release |
| Human embryonic stem cell–derived immunity- and matrix-regulatory cells (hESC-IMRCs) | Stem cell therapy based mitigation of acute lung injury with subsequent pulmonary fibrosis |
| PLN-74809, TD139 | Novel antifibrotics influencing different target molecules of the TGF-β pathway (ɑvβ6 integrin, galectins) |
| ɑvβ6 integrin inhibitor | Blockade of ɑvβ6 integrin-dependent latent TGF-β activation |