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Nano Lett . Host-Directed Virus-Mimicking Particles Interacting with the ACE2 Receptor Competitively Block Coronavirus SARS-CoV-2 Entry

tetano

Editor, Senior Moderator
Nano Lett


. 2024 Mar 11.
doi: 10.1021/acs.nanolett.3c04430. Online ahead of print. Host-Directed Virus-Mimicking Particles Interacting with the ACE2 Receptor Competitively Block Coronavirus SARS-CoV-2 Entry

Pei Zhang[SUP] 1 2 [/SUP], Erik Niemelä[SUP] 2 [/SUP], Sandra López Cerdá[SUP] 1 [/SUP], Pasi Sorvisto[SUP] 2 [/SUP], Jani Virtanen[SUP] 2 [/SUP], Hélder A Santos[SUP] 1 3 [/SUP]



Affiliations
Abstract

Herein, we fabricate host-directed virus-mimicking particles (VMPs) to block the entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into host cells through competitive inhibition enabled by their interactions with the angiotensin-converting enzyme 2 (ACE2) receptor. A microfluidic platform is developed to fabricate a lipid core of the VMPs with a narrow size distribution and a low level of batch-to-batch variation. The resultant solid lipid nanoparticles are decorated with an average of 231 or 444 Spike S1 RBD protrusions mimicking either the original SARS-CoV-2 or its delta variant, respectively. Compared with that of the nonfunctionalized core, the cell uptake of the functionalized VMPs is enhanced with ACE2-expressing cells due to their strong interactions with the ACE2 receptor. The fabricated VMPs efficiently block the entry of SARS-CoV-2 pseudovirions into host cells and suppress viral infection. Overall, this study provides potential strategies for preventing the spread of SARS-CoV-2 or other coronaviruses employing the ACE2 receptor to enter into host cells.

Keywords: SARS-CoV-2; Spike S1 receptor binding domain; angiotensin-converting enzyme 2; microfluidics; virus-mimicking particles.

 
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