Journal
MATTER
Volume 4, Issue 6, Pages 2059-2082Publisher
CELL PRESS
DOI: 10.1016/j.matt.2021.04.005
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Funding
- NIH New Innovator award [1DP2AI144245]
- NSF [1653782]
- UChicago Big Ideas Generator Grant
- NSF Graduate Research Fellowships Program [DGE-1746045]
- NIDDK [RC2DK122394]
- [DP2DA051912]
- Div Of Chem, Bioeng, Env, & Transp Sys
- Directorate For Engineering [1653782] Funding Source: National Science Foundation
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Nanotraps, a new nanomedicine, effectively inhibit SARS-CoV-2 infection by blocking the interaction between the virus and host cells; they demonstrate excellent biosafety in vitro and in vivo; Nanotraps successfully inhibit pseudotyped SARS-CoV-2 infection in live human lung tissue ex vivo.
SARS-CoV-2 enters host cells through its viral spike protein binding to angiotensin-converting enzyme 2 (ACE2) receptors on the host cells. Here, we show that functionalized nanoparticles, termed Nanotraps,'' completely inhibited SARS-CoV-2 infection by blocking the interaction between the spike protein of SARS-CoV-2 and the ACE2 of host cells. The liposomal-based Nanotrap surfaces were functionalized with either recombinant ACE2 proteins or anti-SARS-CoV-2 neutralizing antibodies and phagocytosis-specific phosphatidylserines. The Nanotraps effectively captured SARS-CoV-2 and completely blocked SARS-CoV-2 infection to ACE2-expressing human cell lines and primary lung cells; the phosphatidylserine triggered subsequent phagocytosis of the virus-bound, biodegradable Nanotraps by macrophages, leading to the clearance of pseudo-typed and authentic virus in vitro. Furthermore, the Nanotraps demonstrated an excellent biosafety profile in vitro and in vivo. Finally, the Nanotraps inhibited pseudotyped SARS-CoV-2 infection in live human lungs in an ex vivo lung perfusion system. In summary, Nanotraps represent a new nanomedicine for the inhibition of SARS-CoV-2 infection.
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