Nanotraps for the containment and clearance of SARS-CoV-2

  1. Min Chen
  2. Jillian Rosenberg
  3. Xiaolei Cai
  4. Andy Chao Hsuan Lee
  5. Jiuyun Shi
  6. Mindy Nguyen
  7. Thirushan Wignakumar
  8. Vikranth Mirle
  9. Arianna Joy Edobor
  10. John Fung
  11. Jessica Scott Donington
  12. Kumaran Shanmugarajah
  13. Eugene Chang
  14. Glenn Randall
  15. Pablo Penaloza-MacMaster
  16. Bozhi Tian
  17. Maria Lucia Madariaga
  18. Jun Huang
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Abstract

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.

Highlights

  • Nanotraps block interaction between SARS-CoV-2 spike protein and host ACE2 receptors

  • Nanotraps trigger macrophages to engulf and clear virus without becoming infected

  • Nanotraps showed excellent biosafety profiles in vitro and in vivo

  • Nanotraps blocked infection to living human lungs in ex vivo lung perfusion system

Progress 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.

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