CHEARS

The relentless coronavirus disease (COVID-19) pandemic quickly prompted the pursuit of novel effective therapeutic agents against the highly virulent SARS-CoV-2 virus. One of the prime targets for researchers is the angiotensin-converting enzyme 2 (ACE2), the primary receptor for SARS-CoV-2 spike glycoprotein (S1 subunit), which mediates viral entry into host cells.

It is already known that ACE2 is pervasive in lung alveolar epithelial cells, renal tubular epithelium, and enterocytes of the small intestine, as demonstrated by large-scale immunohistochemistry, transcriptomics, and proteomics analysis.

Due to the natural positioning of ACE2 on the cell membrane, and considering how membrane with active ingredients can be used to expand our antiviral arsenal, the researchers from the Third Military Medical University in Chongqing (China) attempted to apply the membrane of human cells abundant with ACE2 to cope with SARS-CoV-2.

Developing cell membrane based nanoparticles

The researchers have picked the membrane of human embryonic kidney-239T cells highly expressing human ACE2 receptor (HEK-293T-hACE2) to prepare cell membrane-based nanoparticles after analyzing the ACE2 content in five different human cells.

In short, HEK-293T-hACE2 cells were processed by repeated freezing and thawing in order to separate the membrane, which was broken by sonication, and subsequently applied to fabricate cell membrane-based nanoparticles using a classical extrusion method.

Moreover, to appraise the bioactivity of HEK-293T-hACE2 nanoparticles, the researchers have initially immobilized biotinylated SARS-CoV-2 S1-RBD on Sartorius streptavidin biosensors and then analyzed the recruitment of cell membrane-based nanoparticles by biolayer interferometry.

Efficient restriction of SARS-CoV-2 adherence

The antiviral activity and mechanism of action of this nanomaterial were explored in depth with the use of pseudovirus neutralization assay, spike adhesion experiment, as well as proteomics analysis. Finally, the toxicity of HEK-293T-hACE2 nanoparticles has been evaluated by a mouse experiment.

Interestingly, SARS-CoV-2 S1 can translocate to the cytoplasm and affect the cell metabolism, which is also inhibited by HEK-293T-hACE2 nanoparticles", study authors further explain. "This biocompatible membrane nanomaterial is sufficient to block the adherence of SARS-CoV-2 D614G-S1 mutant to sensitive cells", they add.

As a result of the spike recruitment, HEK-293T-hACE2 nanoparticles adsorbed SARS-CoV-2 S pseudovirions on the material surface. They successfully blocked viral entry into the cytoplasm – enabling a rather inspiring type of host cell protection from the viral infection.

And indeed, since there is still a lack of effective measures to treat COVID-19, this type of biocompatible and easy-to-achieve nano-antagonist may be a rather convenient therapeutic candidate for curbing the dire effect of SARS-CoV-2 spread. Naturally, further studies with a more practical, in vivo approach are needed,

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Source: Medical net