Apelin-potential therapy for COVID-19?

Abstract

We believe that, in parallel to the attempts for direct blockade of the SARS-CoV-2 penetration into host cell and repurposing drugs, finding new therapeutic strategies for patients with lung injury or cardiovascular complications/coagulopathies associated with COVID-19 should be paid particular attention. Apelin or its receptor agonists are of great potential treatment for COVID-19 through suppressing angiotensin-converting enzyme (ACE) and angiotensin II (Ang-II) production, as well as, down-regulating angiotensin receptor 1 (AT1R) and ACE2 up-regulation. These drugs have potential to improve acute lung injury and cardiovascular/coagulopathy complications in COVID-19 which are associated with elevated Ang-II/Ang(1-7) ratio.

Abnormal apelin-ACE2 and SGLT2 signaling contribute to adverse cardiorenal injury in patients with COVID-19

“…Our previous published work demonstrated that Ang II-induced inflammation, oxidative stress, cardiorenal fibrotic remodeling and dysfunction were exacerbated in ACE2-deficient mice [ 21 , 22 ]. Besides, apelin has been demonstrated to protect against acute respiratory distress syndrome, cardiovascular injury and endothelial inflammation through activating the ACE2/Ang-(1–7)/Mas axis and blocking the Ang II-AT1R actions, indicating that apelin/ACE2 signaling could be a promising therapeutic target in ameliorating cardiorenal injuries during COVID-19 [ 23 ]. In this study, we demonstrated decreased apelin-ACE2 signaling and increased levels of pro-inflammatory factors and fibrosis-related genes in post-MI HF rats, AKI and ACE2 KO mice.…”

ACE2: The Major Cell Entry Receptor for SARS-CoV-2

“…Furthermore, beyond the RAAS and KKS, ACE2 has been shown to act on other substrates such as apelin-13/17, neurotensin (1-11), β-casomorphin-(1-7), dynorphin A (1-13), and ghrelin among others [86]. These substrates are interesting potential therapeutic targets for COVID-19 [77], but we will not discuss them because their involvement in COVID-19 is still highly speculative.…”

ACE2 in the second act of COVID‐19 syndrome: Peptide dysregulation and possible correction with oestrogen

“…These observations may lead to the conclusion that ACE2 down‐regulation in COVID‐19 increases the concentration of higher‐affinity parental apelin peptides, countering the effects of the aggressive branch of the RAAS. Indeed, exogenous administration of apelin has been suggested as a treatment for COVID‐19 27 . However, even though parental apelins have a higher affinity for APJ than metabolised apelins, there is an increasing volume of research suggesting that parental apelin isoforms induce receptor internalisation mediated by β‐arrestin signalling, blunting the effect of high concentrations of parent apelin peptides.…”