RT Journal Article
SR Electronic
T1 Nanotraps for the containment and clearance of SARS-CoV-2
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.02.01.428871
DO 10.1101/2021.02.01.428871
A1 Min Chen
A1 Jillian Rosenberg
A1 Xiaolei Cai
A1 Andy Chao Hsuan Lee
A1 Jiuyun Shi
A1 Mindy Nguyen
A1 Thirushan Wignakumar
A1 Vikranth Mirle
A1 Arianna Joy Edobor
A1 John Fung
A1 Jessica Scott Donington
A1 Kumaran Shanmugarajah
A1 Eugene Chang
A1 Glenn Randall
A1 Pablo Penaloza-MacMaster
A1 Bozhi Tian
A1 Maria Lucia Madariaga
A1 Jun Huang
YR 2021
UL http://biorxiv.org/content/early/2021/02/01/2021.02.01.428871.abstract
AB 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 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 pseudotyped and authentic virus in vitro. Furthermore, the Nanotraps demonstrated 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.HighlightsNanotraps block interaction between SARS-CoV-2 spike protein and host ACE2 receptorsNanotraps trigger macrophages to engulf and clear virus without becoming infectedNanotraps showed excellent biosafety profiles in vitro and in vivoNanotraps blocked infection to living human lungs in ex vivo lung perfusion systemProgress and Potential To address the global challenge of creating treatments for SARS-CoV-2 infection, we devised a nanomedicine termed “Nanotraps” that can completely capture and eliminate the SARS-CoV-2 virus. The Nanotraps integrate protein engineering, immunology, and nanotechnology and are effective, biocompatible, safe, stable, feasible for mass production. The Nanotraps have the potential to be formulated into a nasal spray or inhaler for easy administration and direct delivery to the respiratory system, or as an oral or ocular liquid, or subcutaneous, intramuscular or intravenous injection to target different sites of SARS-CoV-2 exposure, thus offering flexibility in administration and treatment. More broadly, the highly versatile Nanotrap platform could be further developed into new vaccines and therapeutics against a broad range of diseases in infection, autoimmunity and cancer, by incorporating with different small molecule drugs, RNA, DNA, peptides, recombinant proteins, and antibodies.Competing Interest StatementThe University of Chicago is in the process of filing a patent based on some of the findings described in this manuscript.