Supramolecular filaments for concurrent ACE2 docking and enzymatic activity silencing enable coronavirus capture and infection prevention

Caleb F Anderson; Qiong Wang; David Stern; Elissa K Leonard; Boran Sun; Kyle J Fergie; Chang-Yong Choi; Jamie B Spangler; Jason Villano; Andrew Pekosz; Cory F Brayton; Hongpeng Jia; Honggang Cui

doi:10.1016/j.matt.2022.11.027

Supramolecular filaments for concurrent ACE2 docking and enzymatic activity silencing enable coronavirus capture and infection prevention

Matter. 2023 Feb 1;6(2):583-604. doi: 10.1016/j.matt.2022.11.027. Epub 2022 Dec 12.

Authors

Caleb F Anderson^{1

2}, Qiong Wang³, David Stern^{1

2}, Elissa K Leonard⁴, Boran Sun^{1

2}, Kyle J Fergie^{1

2}, Chang-Yong Choi³, Jamie B Spangler^{1

4

5

6}, Jason Villano⁷, Andrew Pekosz^{6

7}, Cory F Brayton⁷, Hongpeng Jia³, Honggang Cui^{1

2

5

8}

Affiliations

¹ Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
² Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD 21218, USA.
³ Division of Pediatric Surgery, Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
⁴ Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
⁵ Department of Oncology and Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
⁶ Department of Molecular Microbiology and Immunology, The Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA.
⁷ Molecular and Comparative Pathobiology, The Johns Hopkins School of Medicine, Baltimore, MD 21205, USA.
⁸ Center for Nanomedicine, The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.

Abstract

Coronaviruses have historically precipitated global pandemics of severe acute respiratory syndrome (SARS) into devastating public health crises. Despite the virus's rapid rate of mutation, all SARS coronavirus 2 (SARS-CoV-2) variants are known to gain entry into host cells primarily through complexation with angiotensin-converting enzyme 2 (ACE2). Although ACE2 has potential as a druggable decoy to block viral entry, its clinical use is complicated by its essential biological role as a carboxypeptidase and hindered by its structural and chemical instability. Here we designed supramolecular filaments, called fACE2, that can silence ACE2's enzymatic activity and immobilize ACE2 to their surface through enzyme-substrate complexation. This docking strategy enables ACE2 to be effectively delivered in inhalable aerosols and improves its structural stability and functional preservation. fACE2 exhibits enhanced and prolonged inhibition of viral entry compared with ACE2 alone while mitigating lung injury in vivo.

Keywords: ACE2; biomaterials; coronavirus; drug delivery; peptide amphiphiles; protein therapeutics; supramolecular filaments.

Abstract

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