Table 1.

An overview on IFN-inducing effects of the antiviral agents. The clinical trial data was gathered on 17 September 2020. Molecular structures of the following drugs are shown as a representative of their classes; for instance, neomycin for aminoglycosides, idarubicin for anthracyclines, and simvastatin for statins. All structures are adapted from PubChem [37].

	Drug/Drug class	Molecular structure	Therapeutic category	Antiviral activity	COVID-19-related studies	Ref.
1	Azithromycin		Antibiotic	Binding to IFNAR1 complex and ISGF3 upregulation/potentiating IFN type I signaling	112 clinical trials specifically on azithromycin/Amplifying the effect of hydroxychloroquine	[38], [39], [40], [41], [42]
2	Aminoglycosides		Antibiotic	ISG induction, suppress replication via binding to promotor RNA	No data found	[38], [43], [44]
3	Nitazoxanide		Amebicide	IFN signaling, autophagy promotion	20 clinical trials in combination with azithromycin or hydroxychloroquine/Inhibits SARS-CoV-2 in cell culture	[38], [45], [46], [47], [48], [49], [50]
4	Niclosamide		Anthelmintic	Inhibition of SARS-CoV 3CL protease, prevention of viral entry	Six clinical trials are enrolling./Suggested as an inhibitor of autophagy and viral replication	[45], [51], [52], [53]
5	Itraconazole		Antifungal	Lanosterol 14α-demethylase inhibition, IFN A/B increase	No data found.	[38], [54]
6	Ribavirin		Antiviral	Inhibition of inosine monophosphate dehydrogenase/RdRp antagonism/causing error catastrophe	Suggested as a COVID-19 therapy/Suggested RdRp antagonist in an in silico study/Twelve clinical trials are enrolling	[45], [52], [55], [56]
7	Anthracyclines		Antibiotic	Enhancement in ISRE activity, inhibition of RNA and DNA synthesis	Idarubicin was suggested as a potent inhibitor of SARS-CoV-2 endoribonuclease by an in silico study	[38], [57], [58], [59], [60]
8	Tamoxifen		Anti-neoplastic	Multistep inflammation inhibitor	One clinical trial in combination with isotretinoin	[45], [52], [61]
9	Gefitinib		EGFR inhibitor	Inhibition of the NF-kB pathway and viral replication	No data found	[38], [62]
10	Trametinib		Multi-kinase inhibitor	Induction of IRF1 and IFN-κ	No data found	[45], [63]
11	Gemcitabine		Anticancer	DNA synthesis inhibition	Predicted to have positive effects through AI analysis	[38], [64], [65]
12	Obatoclax		Anticancer	Suppression of viral endocytic uptake	No data found	[38], [66]
13	Sirolimus		Immunosuppressant	Entry inhibitor, downregulation of CCR5	Suggested in an interactome-based bioinformatics study/Six clinical trials are enrolling	[38], [52], [67], [68]
14	Mycophenolic acid		Immunosuppressant	ISGs upregulation	Recognized as the most potent compound against the envelope protein and nucleocapsid phosphoprotein of SARS-CoV-2 by a docking study	[45], [69], [70]
15	Aspirin		NSAID	COX-2 inhibition, p38 MAPK and MEK1/2 activation	Fourteen clinical trials are enrolling	[38], [52], [71]
16	Indomethacin		NSAID	Production of 2′,5′-OAS, Th1 response enhancement, viral RNA synthesis block	Two clinical trials are enrolling. Opined for use in positive SARS-CoV-2 patients who have no cytokine storm	[38], [52], [72], [73]
17	Metformin		Anti-hyperglycemic	Promoting cells’ insulin sensitivity/JAK/STAT pathway activation	In silico suggestion as an interferer with Acetyl-CoA Carboxylase α gene	[38], [74], [75], [76]
18	Fluoxetine		Antidepressant	JAK/STAT1 activation	Two clinical trials are enrolling	[38], [52], [77]
19	Verapamil		Calcium channel blocker	Cell entry inhibition	Three clinical trials are enrolling	[38], [52], [78]
20	Statins		Anti-hypercholesterolemia	Prenylation inhibition, reduction of cell-to-cell fusion	Eleven clinical trials are enrolling./Hypothesized to be effective because of immunomodulatory effect and cardiovascular damage.Recommended for use in patients with cardiovascular disease history	[45], [52], [79], [80], [81]
21	Caffeine		CNS stimulant	COX-2, HSP90, and Ras-ERK inhibition	Four clinical trials are enrolling	[45], [52], [82]
22	Glycyrrhizin		Anti-inflammatory	Downregulation of ROS formation, NF-κB, JNK, and p38 MAPK	Suggested as a potential drug because of ACE2 binding, proinflammatory cytokine downregulation, and ROS accumulation inhibition	[45], [83], [84]
23	Berberine		Antiseptic	Stimulation of Th1 response and IFN-γ	One clinical trial is enrolling	[45], [85], [86]

2′, 5′-OAS: 2′-5′-oligoadenylate synthase/ACE: angiotensin converting enzyme/CoA: co-enzyme A/COVID-19: coronavirus disease 2019/COX: cyclooxygenase/ERK: Extracellular signal-regulated kinase/HSP90: heat shock protein 90/IFN: interferon/IFNAR: type I interferon receptor/IRF: interferon-regulatory factor/ISG: interferon-stimulated gene/ISGF: interferon-stimulated gene factor/ISRE: interferon-stimulated response element/JAK: Janus kinase/MEK: mitogen-activated protein kinase/NF-κB: nuclear factor-κB/RdRp: RNA-dependent RNA polymerase/ROS: reactive oxygen species/SARS-CoV: severe acute respiratory syndrome coronavirus disease/STAT: transducer and activator of transcription/Th: T helper cell.