Extracellular Vesicles Displaying ACE2 Can Prevent Infection by SARS-CoV-2 Spike-Protein-Pseudotyped Lenti Virus; ACE2-EVs Are Up to 1500X As Effective As Soluble ACE2; Infection Prevention Further Enhanced by Inclusion of TMPRRS2 in EV Surface

In a non-final, non-peer-reviewed, pre-print* article, published online on July 8, 2020 on the pre-print portal bioRxiv,* researchers in Paris, France, have shown that extracellular vesicles (EVs) bearing the surface receptor ACE2 (angiotensin-converting enzyme 2), to which the spike (S) protein of SARS-CoV-2 virus binds when infecting human cells, may serve as decoys to the invading virus because such EVs effectively prevent infection of ACE2-bearing cells by a SARS-Co-V2 S-protein-pseudotyped lenti virus in vitro. The authors note that SARS-CoV-2 entry is mediated in COVID-19 by binding of the viral S protein to the host cell surface receptor ACE2 and subsequent priming by host cell TMPRRS2 (transmembrane protease, serine 2) that allows membrane fusion and viral entry to the cell. The researchers said that the reduction of infectivity correlates positively with the level of EV ACE2 This reduction in infectivity is 500X to 1500X more efficient than is achieved with soluble ACE2, and is further enhanced by inclusion of TMPRRS2 in the EV surface. The researchers conclude that ACE2-EVs represent a potential versatile therapeutic tool to block, not only SARS-CoV-2 infection, but also infections by other coronaviruses that use ACE2 for host cell entry. The open-access article on the bioRxiv portal is titled “Extracellular Vesicles Containing ACE2 Efficiently Prevent Infection by SARS-Cov-2 Spike Protein-Containing Virus” (https://www.biorxiv.org/content/10.1101/2020.07.08.193672v1?fbclid=IwAR07rg3VG3EK0hGxPZBBLbbJlveKekzOb-DkgvgzJk061FD-Jux7q_xRPxo). The co-senior and co-corresponding authors of this open-access article are Mercedes Tkach, PhD; Clotilde Thery, PhD; and Lorena Martin-Jaular, PhD, each of INSERM U932, Institut Curie Centre de Recerche, PSL Research University, Paris, France.
Login Or Register To Read Full Story