Killing Two Birds with One Stone by Administration of Soluble ACE2: A Promising Strategy to Treat Both Cardiovascular Diseases and SARS-CoV-2 Infection.

Fengling Feng,Yanjun Li,Jin Zhao,Jiaoshan Chen,Caijun Sun,Minchao Li

doi:10.3390/v13112243

Fengling Feng, Yanjun Li + Show 4 more

Open Access

https://doi.org/10.3390/v13112243

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Journal: Viruses	Publication Date: Nov 8, 2021
Citations: 4	License type: CC BY 4.0

Affiliation: Sun Yat-sen University

Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters host cells mainly by the angiotensin converting enzyme 2 (ACE2) receptor, which can recognize the spike (S) protein by its extracellular domain. Previously, recombinant soluble ACE2 (sACE2) has been clinically used as a therapeutic treatment for cardiovascular diseases. Recent data demonstrated that sACE2 can also be exploited as a decoy to effectively inhibit the cell entry of SARS-CoV-2, through blocking SARS-CoV-2 binding to membrane-anchored ACE2. In this study, we summarized the current findings on the optimized sACE2-based strategies as a therapeutic agent, including Fc fusion to prolong the half-life of sACE2, deep mutagenesis to create high-affinity decoys for SARS-CoV-2, or designing the truncated functional fragments to enhance its safety, among others. Considering that COVID-19 patients are often accompanied by manifestations of cardiovascular complications, we think that administration of sACE2 in COVID-19 patients may be a promising therapeutic strategy to simultaneously treat both cardiovascular diseases and SARS-CoV-2 infection. This review would provide insights for the development of novel therapeutic agents against the COVID-19 pandemic.

Highlights

The outbreak of coronavirus disease 2019 (COVID-19) has spread rapidly around the world, and become one of the severest public health threats in recent decades
COVID-19 was caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with clinical symptoms ranging from asymptomatic infection, mild disease, severe lung failure, multiorgan damage, and eventually to death [1]
This is because the binding of SARS-CoV-2 to the angiotensin converting enzyme 2 (ACE2) receptors commonly leads to the formation of endosomes, resulting in reducing of the ACE2 expression on the cell surface, causing the renin– angiotensin system (RAS) system to enter into the pro-inflammatory mode, inducing the body to produce more reactive oxygen species, fibrosis, collagen deposition, and producing a series of cytokines such as IL-6 and IL-8 [11]

Summary

Introduction

The outbreak of coronavirus disease 2019 (COVID-19) has spread rapidly around the world, and become one of the severest public health threats in recent decades. Besides of its well-known physiological functions in cardiovascular system, ACE2 has been exploited as a receptor to mediate the entry into host cells of some viruses, including SARS-CoV-2, SARS-CoV, and NL63-CoV [8]. The entry of SARSCoV-2 via the ACE2 receptor often induces a series of detrimental immune responses in the host body, including complement activation, innate immune activation, inflammasome activation, pyroptosis, cytokine storm generation, and so on This is because the binding of SARS-CoV-2 to the ACE2 receptors commonly leads to the formation of endosomes, resulting in reducing of the ACE2 expression on the cell surface, causing the RAS system to enter into the pro-inflammatory mode, inducing the body to produce more reactive oxygen species, fibrosis, collagen deposition, and producing a series of cytokines such as IL-6 and IL-8 [11]. 23-mer peptide derived from α1-helix (SBP1) Screened from five antibacterial peptide databases and a chimeric peptide design approach

Prolonging the Half-Life of sACE2 by Fusion with a Varied Fc Fragment

Optimizing Truncated sACE2 Peptides to Enhance Its In Vivo Safety

Conclusions and Perspective