Abstract
COVID-19 is an ongoing viral pandemic disease that is caused by SARS-CoV2, inducing severe pneumonia in humans. However, several classes of repurposed drugs have been recommended, no specific vaccines or effective therapeutic interventions for COVID-19 are developed till now. Viral dependence on ACE-2, as entry receptors, drove the researchers into RAS impact on COVID-19 pathogenesis. Several evidences have pointed at Neprilysin (NEP) as one of pulmonary RAS components. Considering the protective effect of NEP against pulmonary inflammatory reactions and fibrosis, it is suggested to direct the future efforts towards its potential role in COVID-19 pathophysiology. Thus, the review aimed to shed light on the potential beneficial effects of NEP pathways as a novel target for COVID-19 therapy by summarizing its possible molecular mechanisms. Additional experimental and clinical studies explaining more the relationships between NEP and COVID-19 will greatly benefit in designing the future treatment approaches.
【저자키워드】 Coronavirus disease 2019, nitric oxide, severe acute respiratory syndrome Coronavirus, ACE inhibitors, Angiotensin receptor blockers, neprilysin, interleukin, tumor necrosis factor, renin angiotensin system, endothelial cells, Alzheimer's disease, Endothelin-1, Mas receptor, reactive oxygen species, Angiotensin-converting enzyme, Natriuretic peptides, angiotensin, Angiotensin II Receptor Type 2, Middle East respiratory syndrome, chloroquine/hydroxychloroquine, pulmonary neuroendocrine cells, Heme oxygenase-1, granulocyte-macrophage colony-stimulating factor, COVID-19coronavirus disease 2019, ILInterleukin, MERSMiddle East Respiratory Syndrome, TNFTumor Necrosis Factor, SARS-CoVsevere acute respiratory syndrome coronavirus, NONitric Oxide, HO-1heme oxygenase-1, VEGFvascular endothelial growth factor, vascular endothelial growth factor, ROSreactive oxygen species, ADAlzheimer's disease, MCP-1monocyte chemoattractant protein-1, monocyte chemoattractant protein-1, nuclear factor kappa B, Nrf2nuclear factor erythroid 2–related factor 2, nuclear factor erythroid 2–related factor 2, ACEangiotensin-converting enzyme, Angangiotensin, ET-1Endothelin-1, ACEIACE inhibitors, ALI/ARDSAcute lung injury/Acute respiratory distress syndrome, Acute lung injury/Acute respiratory distress syndrome, ARBsAngiotensin receptor blockers, AT1RAngiotensin II receptor type 1, Angiotensin II receptor type 1, AT2RAngiotensin II receptor type 2, Aββ-amyloid, β-amyloid, BKsBradykinins, Bradykinins, BRBradykinin receptor, Bradykinin receptor, CQ/HCQChloroquine/Hydroxychloroquine, ECsEndothelial cells, eNOSendothelial Nitric oxide synthase, endothelial Nitric oxide synthase, fMLPformyl Methionyl-meucyl-proline, formyl Methionyl-meucyl-proline, GM-CSFGranulocyte-macrophage colony-stimulating factor, GPCRG protein-coupled, G protein-coupled, GRPGastrin-releasing peptide, Gastrin-releasing peptide, MAPK/ERKMitogen-activated protein kinases/ Extracellular signal-regulated kinases, Mitogen-activated protein kinases/ Extracellular signal-regulated kinases, MasRMas receptor, NADPHNicotinamide adenine dinucleotide phosphate (reduced form), Nicotinamide adenine dinucleotide phosphate (reduced form), NEPNeprilysin, NEPiNeprilysin inhibitors, Neprilysin inhibitors, NF-kBNuclear factor kappa B, NPsNatriuretic peptides, NSAIDsNon steroidal anti-inflammatory drugs, Non steroidal anti-inflammatory drugs, PLCb/IP3Phospholipase C beta/inositol trisphosphate, Phospholipase C beta/inositol trisphosphate, PNECsPulmonary neuroendocrine cells, PPARsPeroxisome proliferator activator receptors, Peroxisome proliferator activator receptors, RASRenin angiotensin system, SERMsSelective estrogen receptor modulators, Selective estrogen receptor modulators, STZStreptozotocin, Streptozotocin, TGF-β1Transforming growth factor- β1, Transforming growth factor- β1, 【초록키워드】 COVID-19, Vaccine, SARS-CoV2, therapy, fibrosis, RAS, Repurposed drug, ACE-2, COVID-19 pathogenesis, pathophysiology, humans, pathway, receptors, severe pneumonia, protective effect, clinical study, Evidence, components, molecular mechanisms, effort, therapeutic intervention, pandemic disease, treatment approaches, researcher, Effect, effective, benefit, caused, suggested, pulmonary inflammatory reaction, 【제목키워드】 COVID-19, targeting,