Table 2.
Selected therapeutic drugs and their combinations for COVID-19 in clinical trials.
| Drug/Combination | Administration route/Posological data | Proposed Mechanism of Action against SARS CoV-2 |
Trial Phase | Common Repercussions | References |
|---|---|---|---|---|---|
| Acalabrutinib with supportive care | Oral route/NA | Bruton's tyrosine kinase inhibitor | I | headache, diarrhea | clinicaltrials.gov (2020o) |
| Arbidol (Umifenovir) | Oral route/2 tables per time, 3 times a day for 14–20 days | Antiviral | IV | Drug sensitization in children | clinicaltrials.gov (2020p) |
| Umifenovir, Interferon-β 1a, Lopinavir/Ritonavir, Single Dose of Hydroxychloroquine, Standards of Care |
Anti-viral | IV | NA | clinicaltrials.gov (2020q) | |
| Atorvastatin | Oral route/40 mg | Competitive inhibitor of HMG-CoA reductase | II | diarrhea, heartburn, muscle pains, | Clinicaltrials.gov (2020r) |
| Atzanavir | NA | Protease inhibitor | III | Gastrointestinal upset, nausea | clinicaltrials.gov (2020s) |
| Nitazoxanide and atazanavir/ritonavir | Oral/tablets | Protease inhibitor | II | Gastrointestinal upset, nausea | clinicaltrials.gov (2020t) |
| Avipatadil | 67 μg (nebulized) | inhibit IL6, and TNF-α production | I | Alteration in blood pressure, ECG or heart rate | clinicaltrials.gov (2020u) |
| Azithromycin | Oral route | Prevents translation of mRNA binding with the bacterial ribosome | IV | diarrhea, nausea, abdominal pain, and vomiting | clinicaltrials.gov (2020v) |
| Atovaquone/Azithromycin | Oral route | Antiprotozoal Agents Antiparasitic Agents |
II | clinicaltrials.gov (2020w) | |
| Ivermectin, Azithromycin, Cholecalciferol |
Oral route | Antihelmintic | NA | clinicaltrials.gov (2020x) | |
| Baricitinib | I.V/2 mg | Janus Kinase inhibitor | III | fever, sweating, muscle aches, | clinicaltrials.gov (2020y) |
| BDB-001 | Injection/NA | Toll-like receptor (TLR) against, Immunostimular | II | Nystagmus, dizziness | clinicaltrials.gov (2020z) |
| BLD-2660 | Oral route/NA | Antiviral, Calpains inhibitor | II | diarrhea, nausea, vomiting | (clinicaltrials.gov, 2020a’) |
| Canakinumab | I.V infusion/750 mg (max dose) | Anti-human-IL-1β monoclonal antibody, Prevent IL-6 release | III | Fever, sweating, stomach pain, diarrhea, | (clinicaltrials.gov, 2020b’) |
| CD24Fc | I.V./Single dose at Day 1, CD24Fc, 480 mg, diluted to 100 ml | Immunomodulator, suppress the expression of inflammatory cytokines | III | Safe | (clinicaltrials.gov, 2020c’) |
| Chlorhexidine, povidone-iodine, saline water. | Oral and nasal rinse/5 cc + 20 cc of nasal rinses + oral gargles, for 7 days- 4 times each day (or all three) | Antiseptic, binds with the anionic cell wall of bacteria this, at high concentration causes membrane disruption and cell death | II | Deafness, ARDS Kidney problem, high blood sodium, metabolic acidosis | clinicaltrials.gov, 2020d’ |
| Chloroquine | Oral Route/500 mg TID for 7 days | Antimalarial, lower endosomal PH, prevent glycosylation of ACE2 enzyme | III | mental problems, abdominal cramps, headache, diarrhea, etc. |
clinicaltrials.gov, 2020e’ |
| Chloroquine, telemedicine | Oral route/NA | IV | clinicaltrials.gov, 2020f’ | ||
| CHLORPROMAZINE (CPZ), Standard of Care (SOC) Chlorpromazine |
Oral route/50 mg | Antipsychotics | III III |
Drowsiness, dizziness, dry mouth |
clinicaltrials.gov, 2020g’ clinicaltrials.gov, 2020h’ |
| Clevudine | Oral route/120 mg once a day for 14 days | Antiviral, causes early viral DNA chain termination | II | May cause mitochondrial toxicity, | clinicaltrials.gov, 2020i’ |
| Corticosteroids | Oral route/40 mg q12 h for 5 days | Immunosuppressiveanti-inflammatory, anti-proliferative | NA | Hypertension, psychosis, hyperkalemia, | (clinicaltrials.gov, 2020j’) |
| Deferoxamine | I.V/NA | Iron chelator | II | Fever, vomiting, hearing loss | (clinicaltrials.gov, 2020k’) |
| Dexamethasone | I.V/1 mg/kg/day ivgtt for 7 days | Anti-inflammatory | III | Cataracts, bone loss, bruising, thrush | clinicaltrials.gov, 2020l’ |
| Ebastine | NA | Antihistamine, 2nd generation H1 receptor agoinst | II | Headache, dry mouth and drowsiness | chictr.org.cn (2020b) |
| EIDD-2801 | Oral route/200 mg | Antiviral | II | No severe side effects | clinicaltrials.gov, 2020m’ |
| Favipiravir | Oral route/NA | Inhibit viral RdRp | IV | Harm babies in pregnant women | clinicaltrials.gov, 2020n’ |
| Hydroxychloroquine (HCQ) | Oral route/400 mg | Lower endosomal PH | II | Nausea, vomiting, heart damage. | clinicaltrials.gov, 2020o’ |
| HCQ, Oseltamivir, Azithromycin | Oral route/200 mg; 75 mg; 500 mg | III | clinicaltrials.gov, 2020p’ | ||
| HCQ and Nitazoxanide | Oral route/200 mg; 500 mg | III | clinicaltrials.gov, 2020q’ | ||
| HCQ vs. Azithromycin | Oral route/400 mg; 500 mg | I | clinicaltrials.gov, 2020r’ | ||
| HCQ and favipiravir | NA | II | clinicaltrials.gov, 2020s’ | ||
| Ifenprodil | Oral route/20 mg TID | Anti-inflammatory | III | Can cause lung injury | clinicaltrials.gov, 2020t’ |
| IFX-1 with Best supportive care | I.V/NA | Targets pro-inflammatory | III | acute severe infusion reactions | clinicaltrials.gov, 2020u’ |
| Isotretinoin | Oral route/0.5 mg/kg/day | Down regulator of ACE2 receptor, PLpro inhibitor, increase CD4 count | III | Dry skin, itching, psychiatric disorders | clinicaltrials.gov, 2020v’ |
| Ivermectin | Oral route/a Single dose (3 mg) of Ivermectin | Ivermectin activates glutamate-gated chloride channels; | III | Stomach pain, headache, itching, vomiting, fever | clinicaltrials. gov, 2020w’ |
| Ivermectin, Nitazoxanide | Oral route/200mcg/kg of Ivermectin | Ivermectin activates glutamate-gated chloride channels; nitazoxanide interfere enzyme-dependent electron transfer | III | Stomach pain, headache, itching, vomiting, fever | clinicaltrials.gov, 2020x’ |
| Lenalidomide | Oral route/25 mg | Antiangiogenic agent, interact with the ubiquitin E3 ligase cereblon and target this enzyme to degrade the Ikaros transcription factors IKZF1, IKZF3 | IV | Vomiting, itching, joint pain, thrombosis, pulmonary embolus, hepatotoxicity, bone marrow toxicity etc. | clinicaltrials.gov, 2020y’ |
| Lopinavir/ritonavir | Oral route/200 mg lopinavir, 50 mg ritonavir Oral route/200 mg and 400 mg respectively |
Bind viral proteases | II | Diarrhea, nausea, vomiting, stomach pain | clinicaltrials.gov, 2020z’ |
| Lopinavir/ritonavir, Emtricitabine/tenofovir, raltegravir (RAL) | Oral/Lopinavir/Ritonavir 400/100 mg | III | clinicaltrials.gov, 2020a’’ | ||
| Lopinavir/rit., Ribavirin and Interferon beta-1b | 1 & 2 oral route, 3 S.C injection/400mg/100 mg, 400 mg′ 0.25 mg respectively | II | clinicaltrials.gov, 2020b’’ | ||
| Lopinavir/ritonavir, and HCQ | I.V infusion,/200 mg; oral route/400 mg lopinavir and 100 mg ritonavir; S.C injection, and 44 μg; 400 mg oral route respectively | III | clinicaltrials.gov, 2020c’’ | ||
| Losartan | Oral route/50 mg daily | Angiotensin receptor blocker | II | Diarrhea, insomnia, muscle pain, fetal death | clinicaltrials.gov, 2020d’’ |
| NA-831 | Oral route/30 mg | NA | II | Safer | clinicaltrials.gov, 2020e’’ |
| NA-831, Atazanavir, Dexamethasone |
Oral route/30 mg, 200 mg, 4 mg respectively | NA | III | Safer | |
| Olokizumab | Oral route/64 mg | Block IL-6 | III | side effect due to antimicrobial activity of IL-6 | clinicaltrials.gov, 2020f’’ |
| Piclidenoson | Oral route/ | A3 adenosine receptor against, deregulate Wnt/β-catenin pathway | II | No severe side effects | clinicaltrials.gov, 2020g’’ |
| Prazosin | Oral route | prevent cytokine storm, Alpha-blocker | II | Headache, nausea, blurredness | clinicaltrials.gov, 2020h’’ |
| Remdesivir | I.V infusion/NA | It mimics adenosine and interferes with RdRp | III | Hypertriglyceridemia, | clinicaltrials.gov, 2020i’’ |
| Remicade | NA | TNF-α inhibitor | II | Sinus infections | clinicaltrials.gov, 2020j’’ |
| Ruxolitinib | Oral route/5 mg | Kinase inhibitor | II | Pancytopenia, thrombocytopenia, anemia, neutropenia | clinicaltrials.gov, 2020k’’ |
| Sildenafil citrate | Oral route/0.1 g per day for 14 days | Phosphodiesterase inhibitor | III | Headache, flushing, upset stomach | clinicaltrials.gov, 2020l’’ |
| TAK 981 | Intravenous/60 min infusion (60 mg) | a selective inhibitor of SUMOlysation enzymatic cascade, | II | Potential liver toxicity | clinicaltrials.gov, 2020m’’ |
| Telmisartan | Oral route/40 mg | Angiotensin receptor blocker | II | Tachycardia, bardycardia, hypotension | clinicaltrials.gov, 2020n’’ |
| Oral route/80 mg twice daily | IV | clinicaltrials.gov, 2020o’’ | |||
| Tocilizumab | I.V injection/8 mg/kg (max 800mg/dose) | Immunosuppressive | II | Urinary tract infection, acute pyelonephritis | clinicaltrials.gov, 2020p’’ |
| Tocilizumab, Dexamethasone | Oral route/Tocilizumab: 8 mg/kg, Dexamethasone: 10 mg | Imunosuppressive | II | Urinary tract infection, acute pyelonephritis | clinicaltrials.gov, 2020q’’ |
| Tranexamic acid | Oral route/1300 mg p.o. 3 times/day for 5 days | Antifibrinolytics | II | Rare | clinicaltrials.gov, 2020r’’ |
| Vazegepant (BHV-3500) | Intranasal/10 mg intranasal for 14 days | Anti-inflammatory antagonist | III | Safer | clinicaltrials.gov, 2020s’’ |
| Vitamin-C (ascorbic acid) | Infusion/12 g twice a day for 7 days | Anti-inflammatory, | II | Nausea, abdominal cramps | clinicaltrials.gov, 2020t’’ |
| Vitamin-D (cholecalciferol) | Oral route/400,000 IU | Immunomodulatory; induces secretion of antimicrobial peptides | III | Increase in urination and thirst | clinicaltrials.gov, 2020u’’ |
| XAV-19 | Infusion/0.5 mg per kg | Heterologous glyco-humanized polyclonal antibody (GH-pAb) raised in swine binds spike protein of SARS-CoV-2 | II | Blood transfusion-related risks | clinicaltrials.gov, 2020v’’ |