Decoy ACE2-expressing extracellular vesicles that competitively bind SARS-CoV-2 as a possible COVID-19 therapy

Abstract

The novel strain of coronavirus that appeared in 2019, SARS-CoV-2, is the causative agent of severe respiratory disease, COVID-19, and the ongoing pandemic. As for SARS-CoV that caused the SARS 2003 epidemic, the receptor on host cells that promotes uptake, through attachment of the spike (S) protein of the virus, is angiotensin-converting enzyme 2 (ACE2). In a recent article published by Batlle et al. (Clin. Sci. (Lond.) (2020) 134, 543-545) it was suggested that soluble recombinant ACE2 could be used as a novel biological therapeutic to intercept the virus, limiting the progression of infection and reducing lung injury. Another way, discussed here, to capture SARS-CoV-2, as an adjunct or alternative, would be to use ACE2+-small extracellular vesicles (sEVs). A competitive inhibition therapy could therefore be developed, using sEVs from engineered mesenchymal stromal/stem cells (MSCs), overexpressing ACE2.

Keywords: ARDS; COVID-19; Extracellular Vesicles; SARS-CoV-2; competitive inhibition therapy.

Figure 1. Schematic for ACE2-expressing small EVs binding SARS-CoV-2

Binding of SARS-CoV-2 S protein through ACE2 expressed on MSC-derived sEVs to competitively inhibit binding to ACE2 on alveolar type II cells and thereby limit infection. This could be tested using a human ACE2 transgenic mouse model and as a preliminary proof of concept study using sEVs from the tumour cell line, A549, a known model of alveolar type II cells [26] and thus a ready source of ACE2⁺ sEVs.