Engineered multivalent self-assembled binder protein against SARS-CoV-2 RBD

Dustin Britton; Kamia Punia; Farbod Mahmoudinobar; Takuya Tada; Xunqing Jiang; P Douglas Renfrew; Richard Bonneau; Nathaniel R Landau; Xiang-Peng Kong; Jin Kim Montclare

doi:10.1016/j.bej.2022.108596

Engineered multivalent self-assembled binder protein against SARS-CoV-2 RBD

Biochem Eng J. 2022 Nov:187:108596. doi: 10.1016/j.bej.2022.108596. Epub 2022 Aug 23.

Authors

Dustin Britton¹, Kamia Punia¹, Farbod Mahmoudinobar^{1

2}, Takuya Tada³, Xunqing Jiang⁴, P Douglas Renfrew², Richard Bonneau^{2

5

6

7}, Nathaniel R Landau³, Xiang-Peng Kong⁴, Jin Kim Montclare^{1

8

9

10}

Affiliations

¹ Department of Chemical and Biomolecular Engineering, New York University Tandon School of Engineering, Brooklyn, New York 11201, USA.
² Center for Computational Biology, Flatiron Institute, New York, New York 10010, USA.
³ Department of Microbiology, NYU, Grossman School of Medicine, New York, New York 10016, USA.
⁴ Department of Biochemistry and Molecular Pharmacology, New York University Grossman School of Medicine, New York, New York 10016, USA.
⁵ Center for Genomics and Systems Biology, New York University, New York, New York 10003, USA.
⁶ Courant Institute of Mathematical Sciences, Computer Science Department, New York University, New York, New York 10009, USA.
⁷ Center for Data Science, New York University, New York, New York 10011, USA.
⁸ Bernard and Irene Schwartz Center for Biomedical Imaging, Department of Radiology, New York University School of Medicine, New York, New York 10016, USA.
⁹ Department of Chemistry, New York University, New York, New York 10012, USA.
¹⁰ Department of Biomaterials, New York University College of Dentistry, New York, New York 10010, USA.

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic since December 2019, and with it, a push for innovations in rapid testing and neutralizing antibody treatments in an effort to solve the spread and fatality of the disease. One such solution to both of these prevailing issues is targeting the interaction of SARS-CoV-2 spike receptor binding domain (RBD) with the human angiotensin-converting enzyme 2 (ACE2) receptor protein. Structural studies have shown that the N-terminal alpha-helix comprised of the first 23 residues of ACE2 plays an important role in this interaction. Where it is typical to design a binding domain to fit a target, we have engineered a protein that relies on multivalency rather than the sensitivity of a monomeric ligand to provide avidity to its target by fusing the N-terminal helix of ACE2 to the coiled-coil domain of the cartilage oligomeric matrix protein. The resulting ACE-MAP is able to bind to the SARS-CoV-2 RBD with improved binding affinity, is expressible in E. coli, and is thermally stable and relatively small (62 kDa). These properties suggest ACE-MAP and the MAP scaffold to be a promising route towards developing future diagnostics and therapeutics to SARS-CoV-2.

Keywords: Antibody-mimic; Diagnostic; Protein engineering; SARS-CoV-2; Therapeutic.