Table 2.
Main repurposed drugs for COVID-19.
| Classes of drug used | Main member (s) | Main molecular mechanisms of action | Use Limitations | References |
|---|---|---|---|---|
| Anti-inflammatory agents | Non-steroidal anti-inflammatory drugs (NSIDs)
|
Inhibit cyclooxygenase enzymes (COX-1/COX-2) that mediate the bioconversion of arachidonic acid into prostaglandins (PGs) which, in turn, control inflammation | Increased risk of stroke and myocardial infarction in acute respiratory tract infections, induced nephrotoxicity in susceptible covid-19 patient groups which is exacerbated by fever and dehydration. | [219], [220], [221] |
Corticosteroids
|
Modulate a variety of the inflammatory cytokines (including IL-1, IL-6, IL-8, IL-12 and TNFα), reduce IFN-γ- (IP-10) and MCP-1, potent mediators of the immune inflammatory response | Inhibit synthesis of anti-inflammatory molecules as lipoxins and resolvins, delaying resolution of inflammation with increase susceptibility for secondary infection, stimulation of hypothalamic-pituitary adrenal axis can also induce lymphocytopenia | [24], [219], [260], [261] | |
Specific anti-cytokines
|
Anakinra is IL-1 receptor antagonist and tocilizumab is IL-6 inhibitor, reducing virally driven hyperinflammation | Anakinra increases risk of infection, mainly pneumonia, induce neutropenia since IL-1 is a neutrophil attractant and growth factor and Tocilizumab reduces CRP levels, masking the clinical symptoms | [10], [22], [262] | |
Anti-inflammatory cytokines
|
Suppress inflammatory activity via IL-1 inhibition that produces other proinflammatory cytokines | Inhibition of gamma-interferon production resulting in more viral burden and early dissemination of viral infections | [17], [263] | |
| Chloroquine (CQ) & Hydroxychloroquine (HCQ) | Anti-inflammatory actions by reducing production of the inflammatory cytokines, might interfere with ACE2 receptor glycosylation, thus preventing SARS-CoV-2 binding to target cells and immunomodulatory benefits by affecting cell signaling in viral infections | Its poisoning has been favored with possible life threatening arrythmias in cardiac patients, retinal toxicity has been described with long term administration of CQ and HCQ, may precipitate liver & renal impairment in susceptible patients | [217], [227], [264], [265] | |
| Estrogens | Estrogens
|
Could suppress TMPRSS2 expression in the lung which is essential for SARS-CoV-2 entry, increase Ang-(1–7) production through ER-α- mediated stimulation of ACE1 and ACE2 expression and activity | Male sexual functions regarding erection, spermatogenesis and libido are adversely affected by estrogen exposure, long-term therapy may precipitate hypertension, cerebrovascular stroke and thromboembolism, increased risk of cervical and breast cancer in high risk patients | [235], [237], [238], [266], [267] |
Selective estrogen receptor modulators (SERMs)
| ||||
| Renin-angiotensin system (RAS) blockers | ACE inhibitors
|
Enhancing the ACE-2/ Ang-(1–7)/ Mas axis to increase the production of ang (1–7) which, in turn, can counteract the activity of ACE/ Ang II/ AT1R axis, ARBs may preserve ACE-2 in competition with SARS-CoV-2 entry into the cell | ACE inhibition suppress kininase-II, which may be followed by accumulation of the protrusive mediators (bradykinin and substance P) in the upper respiratory tract or lungs resulting in dry cough and angioedema in susceptible individuals, ARBs may show upregulation in the membrane bound ACE-2 facilitating the coronavirus entry and worsen then its course | [240], [241], [268], [269] |
Angiotensin II type 1 receptor blockers (ARBs)
| ||||
Direct renin inhibitors (DRI)
|
Competitive inhibition of renin, lower the formation of Ang I, and therefore of Ang II and Ang (1–7) reduction in ACE2 expression | Same adverse effects as other RAS blockers mainly cough, contraindicated in old patients with renal or hepatic impairment | [28], [270], [271] |
ACE = Renin Angiotensin System; ACE-1 = Angiotensin Converting Enzyme 1; ACE-2 = Angiotensin Converting Enzyme 2; Ang-(1–7) = Angiotensin 1–7; COX-1 = Cyclooxygenase-1; COX-2 = Cyclooxygenase-2; CRP = C-reactive protein; ER-α = Estrogen receptors alpha; IFN-γ- (IP-10) = Interferon gamma-Induced Protein 10; IL = Interleukin; MCP-1 = Monocyte chemoattractant protein 1; TMPRSS2 = Transmembrane Protease Serine 2; TNFα = Tumor Necrosis Factor Alpha.