Table 2.

Molecular pathways involved in SARS‑CoV‑2 infection and pathway-based therapeutic targets.

Signaling pathways	Molecular targets	Therapeutic agents	Diseases	Reference
Renin-angiotensin system (RAS) pathway	ACE2	NAAE (ACE2 inhibitor), rhACE2 (GSK2586881)	SARS-CoV, ARDS	[1], [2]
	TMPRSS2	Exogenous estrogen, Camostat mesylate, Aprotinin, MI-432, MI-1900, Nafamostat	SARS-CoV-2 infection	[3], [4]
	ACE	Lisinopril, Enalapril, Vitamin D3	Heart/Kidney, Heart, Kidney, SARS-CoV-2	[5], [6]
	AT1R	Losartan/Olmesartan, Losartan, Irbesartan, Telmisartan, Olmesartan	Heart/Kidney, Aorta, Heart, Kidney, SARS-CoV-2 infection	[5], [7]
	ADAM17	A1AT, TIMP-3, TAPI-1, siRNA, Apratastat, TMI-1	Chronic obstructive pulmonary disease, SARS-CoV-2 infection	[8], [9], [10]
IL-6-JAK/STAT	IL-6	Sirukumab, FC-sgp130, Olokizumab, MAb 1339, CNTO328, Clazakizumab, Oroxylin A, ALX-0061, Siltuximab	Cardiovascular disease, RA, Multiple myeloma, prostate cancer, Renal cell carcinoma, B-cell Non-Hodgkin lymphoma, Ovarian cancer, Non-small cell lung cancer, SARS-CoV-2 infection	[11], [12], [13], [14]
	IL-6R	Tocilizumab, Sarilumab, ERBF, SANT-7, sgp130FC, NRI	Leukaemia, Metastatic breast cancer, Pancreatic cancer, RA, Multiple myeloma, tumor cell line	[12], [15], [16], [17], [18]
	JAK	TG101209, WP1066, CEP 3379, Sorafenib, Tofacitinib, Ruxolitinib, AG490	Lung cancer, Gastric cancer, Colorectal cancer, Glioblastoma, Cardiovascular disease, Pancreatic cancer	[11], [19], [20], [21], [22], [23]
	gp130	B-P4, Madindoline A, SC144, Raloxifene, Bazedoxifene, LMT-28	Inflammatory hepatocellular adenoma, Non-small cell lung cancer xenograft, Ovarian cancer, Breast cancer, Erythroleukemia	[24], [25], [26], [27], [28]
	JAK/STAT signaling	Trichostatin A, Bufalin, Baricitinib, Ruxolitinib, Tofacitinib	Experimental CRC, SARS-CoV-2 infection	[29], [30]
	STAT3	JSI-124, Stattic, Eriocalyxin B, S3I-201, STA-21, OBP-31121, OBP-51602, AZD9150, C188–9	B-leukemia, Breast and liver cancer, prostate cancer, Cardiovascular disease, Hepatocellular carcinoma, Multiple myeloma, NHL, AML, ALL, CML, Nasopharyngeal carcinoma, Advanced solid tumors, Metastatic HNSCC, Advanced stage lymphomas, Advanced stage pancreatic cancer, NSCLC, CRC	[11], [15], [31], [32], [33], [34], [35]
	SOCS3	SOCS3	Cardiovascular disease
IL-1B signaling	IL-1	Anakinra	SARS-CoV-2 infection	[30], [36]
TNF signaling	TNF-γ	Baricitinib	SARS-CoV-2 infection	[36]
	TNF-α	Adalimumab, Etanercept, Infliximab	SARS-CoV-2 infection	[36], [37], [38]
	TNF	Infliximab, Golimumab, Adalimumab	SARS-CoV-2 infection	[30]
IL-6 signaling	IL-6	Tocilizumab, Sarilumab, Baricitinib	SARS-CoV-2 infection	[30], [36]
IFN-γ signaling	IFN-γ	Emapalumab	SARS-CoV-2 infection	[30]
IL-17	IL-17	Fedratinib, Secukinumab, Netakimab	Myelofibrosis, SARS-CoV-2 infection	[39], [40]
GM-CSF	GM-CSF	Mavrilimumab, Lenzilumab, Tocilizumab	SARS-CoV-2 infection	[41]
NF-κB signaling pathway	Inhibit translocation of the RELA	CAPE	SARS-CoV	[42], [43]
	Inhibit IKK complex	Bay 11–7082, Parthenolide, Gabexate mesilate, resveratrol	SARS-CoV, lipopolysaccharide (LPS)-induced tissue injury, allergic asthma	[42], [44], [45], [46]
	NF-κB cascade	Dexamethasone, Hydroxychloroquine, Macrolide antibiotics, N-acetylcysteine	SARS-CoV-2 infection	[47]
TLR signaling pathway	Inhibitor TLR3, TLR4, TLR7 and TLR8	Ulinastatin, M5049, Chloroquine, Hydroxychloroquine, Polyinosinic: polycytidylic acid, INNA-051	SARS-CoV-2 infection	[48], [49], [50], [51], [52], [53], [54], [55]
mTOR signaling pathway	mTORC1	Sirolimus, Rapamycin, Azithromycin, Niclosamide	SARS-CoV-2, H1N1, H3N2	[56], [57], [58], [59]
	mTOR	Metformin, Buformin, Phenformin	Influenza	[57]
P38 MAPK signaling pathway	P38	Chloroquine, SB203580, Dilmapimod, Losmapimod	HCoV-229E, Acute lung injury, Hypercholesterolemic patients	[60], [61], [62]
Kallikrein pathway	B1R	Safotibant	reversion acute inflammatory pain induced by carrageenan, and persistent inflammatory pain induced by CFA	[63]
	B2R	Icatibant	Hereditary angioedema, SARS-CoV-2 infection	[64], [65]
	Kallikrein	Lanadelumab, C1 esterase inhibitor	Hereditary angioedema, SARS-CoV-2 infection	[65], [66]
HIF-1 signaling pathway	HIF prolyl hydroxylase	HIF prolyl hydroxylase inhibitors: FG-4592 (Roxadustat)	SARS-CoV-2 infection	[67]
Cell death signaling pathway	NLRP3 inflammasome	MCC950, oridonin Ang (1–7) or heme oxygenase 1 activators	Inflammatory diseases SARS-CoV-2 infection	[68], [69]
	Inflammasome activation signaling	Anakinra, Tocilizumab and IFN-β	SARS-CoV-2 infection	[69]
	RIPK3 and MLKL	Zharp-99, necrosulfonamide, GSK843, GSK872	Inflammatory injury, cancer metastasis	[70], [71]