Table 1.

Compounds downregulating vimentin expression

Name of molecule	Type	Effects	Modes of action	Models	Reference
17-DMCHAG	Geldanamycin derivative	Antimigratory; antiproliferative	Inhibits HSP90; induces the proteasome-dependent degradation of androgen receptor	Human prostate cancer cells; tumour-bearing mice	79
Alpha-lipoic acid*	Acid; antioxidant	Inhibitor of EMT; antiproliferative	Inhibits TGF-ß; activates AMPK and downregulates mTOR-S6 signalling	Human thyroid cancer cells; tumour-bearing mice	80
Apigenin*†	Flavonoid derivative	Antiapoptosis; pro-proliferative; antifibrotic	Decreases miR-34a	Mouse mesothelial peritoneal cells	81
Berberine*	Alkaloid derivative	Inhibitor of EMT; antiproliferative	Decreases PI3/AKT, Ras-Raf-ERK and TGF-ß1 signalling	Mouse neuroblastoma cells	82
Bergamottin	Furanocoumarin derivative	Inhibitor of EMT; antimigratory	Decreases PI3K/AKT/mTOR, TGF-ß signalling	Human lung adenocarcinoma cells	83
Beta-asarone	Phenylpropanoid derivative	Inhibitor of EMT; antimigratory	Decreases hnRNP A2/B1, MMP-9, p-STAT3 expression	Human glioma cells	84
Beta-lapachone	Quinone derivative	Inhibitor of EMT; antimigratory; proapoptosis	Induces apoptosis through caspase-3, -8 and -9 activation and poly(ADP-ribose) cleavage; decreases MMP-2 and MMP-9	Mouse colon cancer cells; tumour-bearing mice	85
BHX	Pyrazoline derivative	Inhibitor of EMT; antimigratory; proapoptosis	Inhibits Wnt/β-catenin signalling	Human breast cancer cells; tumour-bearing mice	86
BMS345541	Selective I kappa B kinase inhibitor	Inhibitor of EMT; anti-inflammatory	Inhibits NF–κB/RelA pathway	Human epithelial cells; polyinosinic–polycytidylic acid-treated mice	87
Chrysin*	Flavonoid derivative	Inhibitor of EMT; antimigratory	Reduces MMP-2 activity; induces zona occludens protein-1 and occludin expression	Human renal epithelial cells; db/db mice	88
Chrysotobibenzyl		Inhibitor of EMT; antimigratory	Decreases integrins (β1, β3, αν), p-FAK, p-AKT, caveolin-1 expression	Human lung cancer cells	89
Cisplatin	Anticancer	Inhibitor of EMT; antimigratory; antiproliferative	Reduces YAP activity	Human colon cancer cells; tumour-bearing mice	90
Compound 11	Selective class I HDAC inhibitor	Inhibitor of EMT; antiproliferative	Decreases p-AKT, p-ERK activity	Human colorectal cancer cells; tumour-bearing mice	91
Curcumin*	Polyphenolic compound	Inhibitor of EMT; antimigratory; antiproliferative	Decreases TGF-ß/Smad2/3 signalling	Human thyroid cancer cells	92
Cypripedin	Phenanthrenequinone derivative	Inhibitor of EMT; antimigratory	Decreases AKT/GSK-3β signalling	Human lung cancer cells	93
D-4F	Apolipoprotein A-I mimetic	Inhibitor of EMT; antifibrotic	Inhibits TGF-ß1	Human alveolar epithelial cells	94
Dehydroepiandrosterone	Steroid	Inhibitor of EMT; antimigratory	Decreases N-cadherin and Snail expression	Human breast cancer cells; tumour-bearing mice	95
Dictamnine	Alkaloid	Inhibitor of EMT; antiproliferative; proapoptosis	Decreases mTOR/p70S6K/eIF4E and MAPK signalling	Human lung cancer cells	96
Ginsenoside Rg3*†	Steroidal saponin	Inhibitor of EMT; antimigratory; proapoptosis	Inhibits LncRNA colon cancer-associated transcript 1 expression and PI3K/AKT signalling; inhibits MAPK and NF–κB signalling	Human colorectal cancer cells; lung cancer cells; tumour-bearing mice	97 98
Hydrogen sulfide*†	–	Inhibitor of EndMT; decrease ER stress; vasodilator; cardioprotective	Decreases Smad2 and Src signalling	Human umbilical vein endothelial cells	99
Hydroxygenkwanin	Flavonoid derivative	Antimigratory; antiproliferative	Activates p21 signalling	Human oral squamous cell carcinoma	44
Icariin*†	Flavonoid derivative	Antimigratory; antiproliferative; proapoptosis	Inhibits PI3K, AKT and MEK/ERK signalling; decreases miR-625-3p and MMP-9 expression	Human thyroid cancer cells	100
Icariside II	Flavonol glycoside	Inhibitor of EMT; antimigratory	Inhibits NF-κB and AKT/GSK-3ß signalling	Human lung cancer cells; tumour-bearing mice	101
Inositol*†	Lipid	Inhibitor of EMT; antimigratory	Inhibits PI3K/AKT and NF-κB signalling	Human breast cancer cells	102
Melatonin*†	Hormone	Inhibitor of EMT; antimigratory; antiproliferative	Inhibits PI3K/AKT signalling; decreases MMP-2, MMP-9, NF-κB p65 expression	Human ovarian cancer cells; gastric cancer cells; tumour-bearing mice	103 104
Metapristone*	RU486 derivative	Antimigratory; antiproliferative; proapoptosis	Decreases AKT and ERK phosphorylation and Bcl-2; upregulates total p53 and Bax expression	Mouse skin melanoma cells	105
Metformin*†	Biguanide derivative; antidiabetic	Inhibitor of EMT; antimigratory	Downregulates HIF-1alpha, CAIX, miR-34a, SNAIL1 and ZEB1; upregulates miR-200a, miR-200c and miR-429	Human cervical squamous cancer cells; human colorectal cancer cell	106 107
Moscatilin	Bibenzyl derivative	Inhibitor of EMT; proapoptosis	Decreases ERK and AKT activity; downregulates caveolin-1 level	Human lung cancer cells	108
N-acetylcysteine*	Antioxidant	Reduce fibrosis; anti-inflammatory	Enhances antioxidant enzyme activities; downregulates oxidising enzymes’ expression	Crystalline silica-induced pulmonary fibrosis mice model	109
Niclosamide*†	Antihelminthic	Inhibitor of EMT; antimigratory	Inhibits Wnt/β-catenin signalling	Human oral squamous cell carcinoma	110
Norcantharidin	Cantharidin derivative	Inhibitor of EMT; antimigratory	Inhibits αvβ6-ERK-Ets1 signalling	Human colon cancer cells	111
Osthole*	Coumarin derivative	Inhibitor of EMT; antimigratory; antiproliferative; proapoptosis	Decreases MMP-2, MMP-9, Smad-3, Snail-1, Twist-1 expression	Human renal cell carcinoma	112
PAC*	Curcumin analogue	Inhibitor of EMT; antimigratory; antiproliferative	Inhibits JAK2/STAT3, AKT/mTOR and MEK/ERK signalling; inhibits STAT3/cyclin D1 pathway	Human colorectal cancer cells; tumour-bearing mice	113
Palbociclib	Selective CDK4/6 inhibitor	Inhibitor of EMT; antimigratory	Inhibits c-Jun/COX-2 signalling	Human breast cancer cells; tumour-bearing mice	114
Pargyline	Lysine-specific demethylase 1 inhibitor	Inhibitor of EMT; antimigratory	Reduces prostate-specific antigen	Human prostate cancer cells; tumour-bearing mice	115
Physcion	Anthraquinone derivative	Inhibitor of EMT; antimigratory	Activates ROS/AMPK/GSK3β signalling; inhibits SOX2	Human colorectal cancer cells	116
Pterostilbene*†	Antioxidant	Inhibitor of EMT; antimigratory	Reduces Src/Fak signalling; upregulates miR-205 expression	Human breast cancer cells; tumour-bearing mice	117
Salidroside*	Glucopyranoside derivative	Inhibitor of EMT; antimigratory; antiproliferative	Downregulates miR-891b expression; inhibits PI3K/AKT/mTOR and NF-κB signalling	Wilms' tumour cells; mouse prostate cancer	118
Selenium*†	Metal	Inhibitor of EMT	Downregulates genes involved in cellular migration, inflammation and mesenchymal markers; upregulates genes involved in epithelial markers	Human prostate	119
Simvastatin*†	Statin	Inhibitor of EMT; antifibrotic	Decreases Toll-like receptor 4 and NF-κB signalling	Human biliary epithelial cells	120
Sinomenine*†	Alkaloid	Antimigratory; antiproliferative	Downregulates miR-23a expression; inhibits PI3K/AKT and JAK/STAT signalling	Human prostate cancer cells	121
Swainsonine	Indolizidine alkaloid	Antimigratory; antiproliferative; proapoptosis	Downregulates miR-92a, inhibits PI3K/AKT/mTOR signalling	Human glioblastoma cells	122
Tanshinone IIA*†	Lipophilic compound	Inhibitor of EMT; antimigratory; antiproliferative	Inhibits STAT3-CCL2 signalling	Human bladder cancer cells	123
Tetramethylpyrazine nitrone	Tetramethylpyrazine derivative	Reduces brain infarction; preserves neurological function	Decrease expression of neuroinflammatory markers	Cynomolgus macaques brain ischaemic stroke model	124
Tetrandrine	Alkaloid	Inhibitor of EMT; antimigratory	Reduces glioma-associated oncogene family zinc finger 1 (Gli-1) expression	Human bladder cancer cells	125
Toosendanin	Alkaloid	Inhibitor of EMT; antimigratory; antiproliferative	Inhibits AKT/mTOR signalling	Human pancreatic cancer cells; tumour-bearing mice	126
Triptolide*†	Diterpenoid derivative	Antifibrotic	Inhibits TLR4-induced NF-κB/IL-1β immune pathway; inhibits NF-κB/TNF-α/VCAM-1 inflammatory pathway; downregulates TGF-β1/α-SMA/vimentin fibrosis pathway	Diabetic rats	127
Valproic acid*†	Acid	Inhibitor of EMT; antiproliferative	Downregulates Smad4 expression; upregulates transcriptional intermediary factor-1γ (TIF1γ) expression	Human prostate carcinoma cells; tumour-bearing mice	128 129
Wogonin*	Flavonoid derivative	Inhibitor of EMT; antimigratory	Inhibits IL-6/STAT3 signalling pathway	Human alveolar adenocarcinoma cells	130

A selection of compounds downregulating vimentin expression and their major cellular and molecular effects. Some of these molecules already have FDA approval, thus can be immediately used to set up clinical trials against COVID-19.

*Indicates the compounds have been referenced by the FDA; the latter group of drugs is briefly discussed in the text.

†Indicates the compounds that have been reported to play a role in acute lung injury.

AMPK, AMP-activated protein kinase; ANG, Angiotensin; Bax, Bcl-2–associated X; Bcl-2, B-cell lymphoma 2; CCL2, Chemokine ligand 2; 17-DMCHAG, 17-(6-(3,4-dimethoxycinnamamido)hexylamino)-17-demethoxy-geldanamycin; eIF4E, Eukaryotic translation initiation factor 4E; EMT, epithelial to mesenchymal transition; EndMT, endothelial to mesenchymal transition; ER, endoplasmic reticulum; ERK, Extracellular signal-regulated kinase; FAK, Focal adhesion kinase; FDA, Food and Drug Administration; GSK-3, Glycogen synthase kinase-3; HDAC, Histone deacetylase; HIF, Hypoxia Inducible Factor; hRNP, Heterogeneous Nuclear Ribonucleoprotein; HSP, Heat Shock Protien; IL, Interleukin; JAK2, Janus kinase 2; LncRNA, Long noncoding RNAs; MAPK, Mitogen-activated protein kinase; MMP, Matrix metallopeptidase; mTOR, Mechanistic target of rapamycin; NF-κB, nuclear factor-kappa B; PEA3, polyoma enhancer activator 3; PI3K, Phosphatidylinositol 3-kinase; ROS, Reactive oxygen species; SMA, Smooth muscle actin; Smad, small mothers against decapentaplegic transcription factor; STAT3, Signal transducer and activator of transcription 3; TGF, Transforming growth factor; TLR4, Toll-like receptor 4; TNF, Tumor necrosis factor; VCAM, Vascular cell adhesion molecule; YAP, Yes-associated protein.