Table 4.

Some of the candidate drugs have already been introduced or validated by various other studies, including in-silico, preclinical, and clinical trials.

No	Drug category	Drug name/ID	Active against	The possible mechanism in COVID-19 treatment	Type of validation by other studies against SARS-CoV-2			Reference
					Another in-silico	Preclinical studies (in vitro, in vivo)	Clinical trials, Case reports, Retrospectives
1	Antiviral	Raltegravir (DB06817)	•Inhibits the activity of HIV integrase	•In-silico against multi-target viral proteins, including 3CL-protease	Yes			Kumar [41]
								Mohamed [42]
2	Antiviral	Indinavir (DB00224)	•HIV protease inhibitor	•In-silico against vial 3CL-protease •Limited toxicity	Yes			Dong [10]
								Chang [9]
3	Antiviral	Dolutegravir (DB08930)	•HIV-1 integrase inhibitor •Blocks strand transfer step of INSTI.	•Against 2'-O-ribose methyltransferase •Predicted by MT-DTI deep learning •Against 3CL-protease.	Yes			Beck [39]
								Khan [40]
4	Anti bacterial	Eravacycline (DB12329)	•Gram-negative, gram-positive aerobic, and facultative bacteria •Binds to the bacterial 30S ribosomal subunit.	•Potential inhibitor of SARS-CoV-2 main protease	Yes			Wang [43]
5	Anti-inflammatory	Hesperidin (DB04703)	•Treatment of influenza A virus (in vitro), upregulate P38, JNK, autonomous immunity	•In-silico affinity against ACE2 •In-silico affinity against SARS-CoV-2 3CLpro •In-silico affinity against SARS-CoV-2 papain-like protease	Yes			[51]
								[54]
								[19]
								[53]
								[48]
								[49]
								[50]
								[52]
6	Anti-inflammatory	Diosmin (DB08995)	•Treats venous disease •Hyperglycemia •Nutrition supplement •Anti-neurodegenerative. (in rats)	•In-silico affinity against SARS-CoV-2 Mpro	Yes			Adem [48]
7	Anti-inflammatory	Rutin (DB01698)	•Capillary fragility. •In-silico affinity against SARS-CoV-2 Helicase (Nsp13) •In-silico affinity against SARS-CoV-2 Mpro	•In-silico affinity against SARS-CoV-2 Helicase (Nsp13) •In-silico affinity against SARS-CoV-2 Mpro	Yes			Adem [48]
								Shanno [103]
								Wu [52]
								Das [50]
8	Anti-allergic/asthmatic	Cromoglicic acid (DB01003)	•Inhibits release from sensitized mast cells. •Prophylactic in asthma •Therapeutic role in influenza A (H5N1) infection in Balb/c •In-silico affinity against SARS-CoV-2 Nsp16	•Reduce the release of cytokines •Alleviate inflammatory cells infiltration in the lungs. •In-silico affinity against SARS-CoV-2 Nsp16	Yes			Han [60]
								Shankar [61]
9	Anti-allergic/asthmatic	Montelukast (DB00471)	•Cysteinyl leukotriene (cysLT) receptor antagonist (LTRA) •Suppress oxidative stress	•Anti-inflammatory •Reduce cytokine production			NCT	Fidan and Aydoğdu [57]
							04389411
							Phase III
10	Cardio vascular	Telmisartan (DB00966)	•Angiotensin II receptor antagonist (ARB) •Decrease angiotensin 1–7 •Lower angiotensin II on lung interstitium	•Inhibiting of endocytosis of virus •Decrease apoptosis			NCT	Rothlin [104] Gurwitz [105]
							04360551
							Phase II
							NCT 04355936
							Phase II
11	Cardio vascular	Avatrombopag (DB11995)	•Thrombopoietin receptor agonist •Increases platelet number, but not platelet activation	•Predicted to bind to ACE and ACE2 PD regions in-silico •More stable binding than angiotensin II (energy > 6.0 kcal/mol).	Yes			Sajib [64]
12	Cardio vascular Cardio vascular	Azilsartan medoxomil (DB08822)	•Angiotensin II receptor antagonist •There are no data on the effects of ARBs and ACEIs on lung ACE2 expression either in animal models or humans	•Angiotensin II receptor blocker, so attenuate the virus entry •An ARB prevented aggravation of acute lung injury in mice infected with SARS •Binds in-silico to SARS-CoV-2 spike	Yes			Sato et al. [106]
					Review
								Kai and Kai [65]
					Hypothesis
								[107]
13	Cardio vascular	Conivaptan (DB00872)	•Inhibits vasopressin receptor •Treatment of hyponatremia	•Binding affinity to both 3-CLprotease (Nsp5) and nsp8 site of RdRp	Yes			[52]
								[108]
								[109]
14	Cardio vascular	Eltrombopag (DB06210)	•Treat low blood platelet counts (e.g. in ITP) •Thrombopoietin Receptor Agonist •Treat Thrombocytopenia •Inhibits HCMV Replication •Used in the treatment of HCV, HIV-1	•Affects SARS-CoV-2 in vitro in Vero cells •Platelets play a role in defense against respiratory viruses •Platelets engulf HIN1 virions and secrete antiviral molecules to destroy virions. (H1N1 is close to SARS-CoV-2)		Vero cells		Jeon et al. [68]
								Arshad et al. [69]
								[67]
								[110]
15	Cardio vascular	Nebivolol (DB04861)	•Beta-adrenergic antagonist, cardiac stimulant, evoking NO	•Binding affinity to viral RdRp	Yes			[111]
								[87]
16	Anti-coagulant	Ticagrelor (DB08816)	P2Y12 receptor antagonism Reduces levels of pro-inflammatory factors inhibits reactivation of platelets, decrease lung injury (by reducing thrombo-inflammatory)	•Reduce DIC development •Anti-bacterial properties are useful in pneumonia, less common sepsis& pulmonary infections	Letter			[72]
								[73]
					Hypothesis
								[74]
								[75]
17	Anti coagulant	Edoxaban (DB09075)	•Selective factor Xa inhibitor •Reduces Coagulation Activity but Not Inflammation Among People With HIV •A direct oral anticoagulant (DOAC)	•High D-dimer levels in novel coronavirus infection (COVID-19); thus, Edoxaban can be useful. •Affects thrombolytic agents.			Yes	Testa et al. [112]
								Baker et al. [113]
18	BPH	Dutasteride (DB01126)	•5-Alpha-Reductase Inhibitor •Off-target effects on androgen receptor due to their similarity to DHT •Treats symptomatic benign prostatic hyperplasia. •Block 5-AR isoform 3, which is expressed in the respiratory epithelium and fibroblasts	•Potential blockers of E channel •Potential SARS-CoV-2 Mpro inhibitor •Androgen decrease is associated with reduced ACE2 •In pneumocytes, TMPRSS2 priming enables viral entry and is associated with AR increase.	Yes			Kroumpouzos [84]
								Chernyshev [79]
								Hosseini et al. [78]
19	BPH	Doxazosin (DB00590)	•Alpha-1 antagonist •Treat benign prostatic hypertrophy	•Potential SARS-CoV-2 Mpro inhibitor (validated by MD trajectory clustering)	Yes			Gupta [80]
20	Impotency	Tadalafil (DB00820)	•PDE5 inhibitor •Treat erectile dysfunction	•Potential against nsp1 (DeepDTA method) •2’-O-methyltransferase potential inhibitor	Yes			Anwar [114]
								Sharma [81]
21	Anti psychotic	Fluspirilene (DB04842)	•Neurotransmitter inhibitor •Used for chronic schizophrenia •An antagonist for Dopamine D2 receptor and 5-HT receptor 2A •Inhibits Voltage-dependent calcium channel gamma-1	•Active against SARS-CoV-2 in-vitro in Vero E6 cell line •Activity against SARS-CoV and MERS-CoV in-vitro		Vero E6 cell line		Weston et al. [115]
								Dyall et al. [116]
22	Anti psychotic	Pimozide (DB01100)	•Diphenylbutylpiperidine •Suppress vocal and motor tics in Tourette syndrome •An antagonist of Dopamine D2, D3 receptor •Inhibits Potassium voltage-gated channel subfamily H member two and Calmodulin	•Binding affinity against 3C-like protease •Is expected to raise endosomal pH. probably lowers the viral entry •An IC50 in inhibiting MPro below 100 μM	Yes	Yes		Vatansever et al. [117]
								Gul et al. [87]
23	Anti psychotic	Lurasidone (DB08815)	•Treats bipolar disorder •An antagonist for Dopamine D2 R, 5-HT receptors 1A, 2A, 7 •An antagonist for Alpha-2C adrenergic receptor	•Binding affinity against NSP8 binding site of SARS-CoV-2 RdRp.	Yes			Gul et al. [87]
24	Antimigraine	Ergotamine(DB00696)	•Alpha-1 selective adrenergic agonist •A calcitonin gene-related peptide antagonist •Affinity for 5-HT, dopamine and noradrenaline receptors	•In-silico affinity for three SARS-CoV-2 proteins •Excess release CGRP leads to an abnormal response of vessels in acute lung injury; •Therefore, CGRP blockade may be helpful in acute lung injuries	Yes			[91]
								[118]
								[90]
25	Anti-diabetic	Linagliptin (DB08882)	•DPP-4 inhibitor •Treats type II diabetes •Chronic hyperglycemia and inflammation lead to abnormalities in the immune system. •Concomitant use of Metformin and Chloroquine has fatal toxicity in mice •DPP4 (CD26) is a serine exopeptidase expressed in many tissues •Alert: it may suppress the immune system too.	•DPP4 probably contributes to SARS-CoV-2 entry •Linagliptin modulates inflammation and is anti‐fibrotic. •It probably prevents the sustained cytokine storm indirectly. •Attenuating effects on inflammation during wound healing in mice.			NCT 04341935	[93]
								[96]
							Phase IV	[97]
							NCT 04371978	[98]
								[99]
							Phase III
								[94]
								[95]
26	Analgesic	Diamorphine (DB01452)	•Acetylated morphine derivative that may be habit-forming •Morphine is agonizts to beta-endorphin, dynorphin, leu-enkephalin, and met-enkephalin consuming high doses affect the brain stem negatively	•Reduce respiratory rate •A complication to the lung. •Therapeutically used in terminal illnesses •Recommended for concomitant painful cancers with moderate COVID-19	Hypothesis			Sawynok [102]
								Marinelli [100]
								Hulin et al. [119]
27	Contraceptive	Drospirenone (DB01395)	•A synthetic progestin •Containing estrogen and progesterone •Control acne, PMDD •Its safety is not apparent, it may increase venous thromboembolism	•Binding affinity for Mpro, PLpro, and RdRp	Yes			Hosseini [78]