Table 3.
Therapeutic targets from signaling pathways.
| Target/Drug | Findings | Ref |
|---|---|---|
| RAS | ||
| ACE2 | ||
| APN01 | Decrease in IL-6 plasma levels | [152] |
| TMPRSS2 | ||
| Camostat mesylate | TMPRSS2 inhibition | [153] |
| Reduced viral infectivity in COVID-19 patients | [153] | |
| Bromhexine hydrochloride | Prevention of viral entry | [153] |
| ER & Golgi | ||
| Cathepsin L | ||
| Ddec-RVKR-CMK | Inhibition of MERS-CoV entry | [154] |
| EST | Inhibition of SARS-CoV entry | [155] |
| MDL-28170 | Inhibition of SARS-CoV entry | [156] |
| Oxocarbazate | Inhibition of SARS-CoV entry | [157] |
| SSAA09E1 | Inhibition of SARS-CoV entry | [158] |
| Immune pathways | ||
| Tociluzimab | Attenuated inflammation, inhibition of IL-6 signaling | [159] |
| Sarilumab | Attenuated inflammation, inhibition of IL-6 signaling | [159] |
| Fedratinib, ruxolinitinib | JAK/STAT inhibitors, attenuated cytokine storm | [159] |
| Fingolimod, Infliximab, adalimumab | S1Pr1 agonist, diminished cytokine storm | [160], [160] |
| Serine protease inhibitors | Blocking of TNF-α, decreased inflammatory process Decreased expression of TNF-α and IL-6 | [160] |
| Anakinra | Inhibition of cytokines | [159] |
| Decreased mortality, reduced hospitalization in phase III | [161] | |
| Quercetin | Suppression of inflammasomes | [159] |
| Flufenamic acid | Selective inhibition of NLPR3 inflammasome | [161] |
| Hypoxia | ||
| Heparin | No improved survival in critically ill COVID-19 patients | [162] |
| Improved survival in noncritically ill COVID-19 patients | [163] | |
| Melatonin | Reduced hypoxia, ferroptosis, hemoglobin denaturation | [164] |
| Calcium pathways | ||
| Bepridil | Reduced infection by prevention of host cell entry | [172] |
| Amlodipine | Reduced infection by prevention of host cell entry | [172] |
| Nifedipine | Reduced infection by prevention of host cell entry | [172] |
| Vitamin D | Downregulated TLR2/TLR4, reduced inflammation | [172] |
| Other pathways | ||
| Apilimod | Clinical evaluation in progress | [166] |
| Tetrandine (TPC2 inhibitor) | Potential inhibition of virus entry and replication | [167] |
| Clinical evaluation in progress | [168] | |
Ddec-RVKR-CMK (ecanoyl-Arg-Val-Lys-Arg-chloromethylketone); ER, endoplasmic reticulum; EST [(23,25)trans-epoxysuccinyl-l-leucylamindo-3-methylbutane ethyl ester]; MDL-28170 (calpain inhibitor III, or Z-Val-Phe-CHO); RAS, renin-angiotensin system; SSAA09E1 {[(Z)-1-thiophen-2-ylethylideneamino] thiourea}; TLR, toll-like receptor; TPC, two-pore channel.