Case, J. B., Winkler, E. S., Errico, J. M. & Diamond, M. S. On the highway to ending the COVID-19 pandemic: are we there but? Virology 557, 70–85 (2021).
CAS PubMed Google Scholar
Dolgin, E. The race for antiviral medicine to beat COVID – and the subsequent pandemic. Nature 592, 340–343 (2021).
CAS PubMed Google Scholar
Wrapp, D. et al. Cryo-EM construction of the 2019-nCoV spike within the prefusion conformation. Science 367, 1255–1260 (2020).
Google Scholar
Jiang, F. et al. Angiotensin-converting enzyme 2 and angiotensin 1-7: novel therapeutic targets. Nat. Rev. Cardiol. 11, 413–426 (2014).
CAS PubMed PubMed Central Google Scholar
Donoghue, M. et al. A novel angiotensin-converting enzyme-related carboxypeptidase (ACE2) converts angiotensin I to angiotensin 1-9. Circ. Res. 87, E1–E9 (2000).
CAS PubMed Google Scholar
Burrell, L. M., Johnston, C. I., Tikellis, C. & Cooper, M. E. ACE2, a brand new regulator of the renin–angiotensin system. Developments Endocrinol. Metab. 15, 166–169 (2004).
CAS PubMed PubMed Central Google Scholar
Hu, B., Guo, H., Zhou, P. & Shi, Z. L. Traits of SARS-CoV-2 and COVID-19. Nat. Rev. Microbiol. 19, 141–154 (2021).
CAS PubMed Google Scholar
Taylor, P. C. et al. Neutralizing monoclonal antibodies for therapy of COVID-19. Nat. Rev. Immunol. 21, 382–393 (2021).
CAS PubMed PubMed Central Google Scholar
Liu, L. et al. Putting antibody evasion manifested by the Omicron variant of SARS-CoV-2. Nature 602, 676–681 (2022).
CAS PubMed Google Scholar
Iketani, S. et al. Antibody evasion properties of SARS-CoV-2 Omicron sublineages. Nature 604, 553–556 (2022).
CAS PubMed PubMed Central Google Scholar
Lei, C. et al. Neutralization of SARS-CoV-2 spike pseudotyped virus by recombinant ACE2-Ig. Nat. Commun. 11, 1–5 (2020).
Google Scholar
Zoufaly, A. et al. Human recombinant soluble ACE2 in extreme COVID-19. Lancet Respir. Med. 8, 1154–1158 (2020).
CAS PubMed PubMed Central Google Scholar
Tsai, T.-I. et al. ACE2-Fc fusion protein overcomes viral escape by potently neutralizing SARS-CoV-2 variants of concern. Antivir. Res. 199, 105271 (2022).
CAS PubMed Google Scholar
Leach, A. et al. A tetrameric ACE2 protein broadly neutralizes SARS-CoV-2 spike variants of concern with elevated efficiency. Antivir. Res. 194, 105147 (2021).
CAS PubMed Google Scholar
Ferrari, M. et al. Characterization of a novel ACE2-based therapeutic with enhanced fairly than diminished exercise towards SARS-CoV-2 variants. J. Virol. 95, e00685-21 (2021).
Tanaka, S. et al. An ACE2 Triple Decoy that neutralizes SARS-CoV-2 reveals enhanced affinity for virus variants. Sci. Rep. 11, 1–12 (2021).
Google Scholar
Svilenov, H. L. et al. Picomolar inhibition of SARS-CoV-2 variants of concern by an engineered ACE2-IgG4-Fc fusion protein. Antivir. Res. 196, 105197 (2021).
CAS PubMed Google Scholar
Chen, Y. et al. Engineered ACE2-Fc counters murine deadly SARS-CoV-2 an infection via direct neutralization and Fc-effector actions. Sci. Adv. 8, 4188 (2022).
Google Scholar
Zhang, L. et al. An ACE2 decoy may be administered by inhalation and potently targets omicron variants of SARS‐CoV‐2. EMBO Mol. Med. 14, e16109 (2022).
CAS PubMed PubMed Central Google Scholar
Aalberse, R. C. & Schuurman, J. IgG4 breaking the foundations. Immunology 105, 9–19 (2002).
CAS PubMed PubMed Central Google Scholar
Yan, R. et al. Structural foundation for the popularity of SARS-CoV-2 by full-length human ACE2. Science 367, 1444–1448 (2020).
CAS PubMed PubMed Central Google Scholar
Bou-Assaf, G. M. et al. Greatest practices for combination quantitation of antibody therapeutics by sedimentation velocity analytical ultracentrifugation. J. Pharm. Sci. 111, 2121–2133 (2022).
CAS PubMed Google Scholar
Tipnis, S. R. et al. A human homolog of angiotensin-converting enzyme: Cloning and purposeful expression as a captopril-insensitive carboxypeptidase. J. Biol. Chem. 275, 33238–33243 (2000).
CAS PubMed Google Scholar
Tian, X., Langkilde, A. E., Thorolfsson, M., Rasmussen, H. B. & Vestergaard, B. Small-angle X-ray scattering screening enhances standard biophysical evaluation: comparative structural and biophysical evaluation of monoclonal antibodies IgG1, IgG2, and IgG4. J. Pharm. Sci. 103, 1701–1710 (2014).
CAS PubMed PubMed Central Google Scholar
Cimmperman, P. et al. A quantitative mannequin of thermal stabilization and destabilization of proteins by ligands. Biophys. J. 95, 3222–3231 (2008).
CAS PubMed PubMed Central Google Scholar
Towler, P. et al. ACE2 X-ray buildings reveal a big hinge-bending movement essential for inhibitor binding and catalysis. J. Biol. Chem. 279, 17996–18007 (2004).
CAS PubMed Google Scholar
Steinmetz, W. E., Carrell, T. N., Peprah, R. B. & Schmatz, S. The conformation and task of the proton NMR spectrum in water of DX600, a bioactive peptide with a random coil conformation. Int. J. Spectrosc. 2011, 296256 (2011).
Huang, L. et al. Novel peptide inhibitors of angiotensin-converting enzyme 2. J. Biol. Chem. 278, 15532–15540 (2003).
CAS PubMed Google Scholar
Dales, N. A. et al. Substrate-based design of the primary class of angiotensin-converting enzyme-related carboxypeptidase (ACE2) inhibitors. J. Am. Chem. Soc. 124, 11852–11853 (2002).
CAS PubMed Google Scholar
Glasgow, A. et al. Engineered ACE2 receptor traps potently neutralize SARS-CoV-2. Proc. Natl Acad. Sci. USA 117, 28046–28055 (2020).
CAS PubMed PubMed Central Google Scholar
Barratt, E. et al. Van der Waals interactions dominate ligand-protein affiliation in a protein binding website occluded from solvent water. J. Am. Chem. Soc. 127, 11827–11834 (2005).
CAS PubMed Google Scholar
Tzeng, S. R. & Kalodimos, C. G. Protein exercise regulation by conformational entropy. Nature 488, 236–240 (2012).
CAS PubMed Google Scholar
Narang, D., James, D. A., Balmer, M. T. & Wilson, D. J. Protein footprinting, conformational dynamics, and core interface-adjacent neutralization ‘hotspots’ within the SARS-CoV-2 spike protein receptor binding area/human ACE2 interplay. J. Am. Soc. Mass Spectrom. 32, 1593–1600 (2021).
CAS PubMed Google Scholar
Humphrey, W., Dalke, A. & Schulten, Okay. VMD: visible molecular dynamics. J. Mol. Graph 14, 33–38 (1996).
CAS PubMed Google Scholar
Šali, A. & Blundell, T. L. Comparative protein modelling by satisfaction of spatial restraints. J. Mol. Biol. 234, 779–815 (1993).
PubMed Google Scholar
Davies, A. M., Jefferis, R. & Sutton, B. J. Crystal construction of deglycosylated human IgG4-Fc. Mol. Immunol. 62, 46–53 (2014).
CAS PubMed PubMed Central Google Scholar
Mehdipour, A. R. & Hummer, G. Twin nature of human ACE2 glycosylation in binding to SARS-CoV-2 spike. Proc. Natl Acad. Sci. USA 118, 2100425118 (2021).
Google Scholar
Group, W. GLYCAM Internet. (Complicated Carbohydrate Analysis Heart, College of Georgia, Athens, GA, 2005–2022).
Case, D. A. et al. AMBER 2020. (College of California, San Francisco, 2020).
Jorgensen, W. L., Chandrasekhar, J., Madura, J. D., Impey, R. W. & Klein, M. L. Comparability of easy potential capabilities for simulating liquid water. J. Chem. Phys. 79, 926–935 (1983).
CAS Google Scholar
Maier, J. A. et al. ff14SB: enhancing the accuracy of protein facet chain and spine parameters from ff99SB. J. Chem. Principle Comput. 11, 3696–3713 (2015).
CAS PubMed PubMed Central Google Scholar
Kirschner, Okay. N. et al. GLYCAM06: a generalizable biomolecular power discipline. carbohydrates. J. Comput. Chem. 29, 622–655 (2008).
CAS PubMed PubMed Central Google Scholar
Manalastas-Cantos, Okay. et al. ATSAS 3.0: expanded performance and new instruments for small-angle scattering knowledge evaluation. J. Appl. Crystallogr. 54, 343–355 (2021).
CAS PubMed PubMed Central Google Scholar
Bernadó, P., Mylonas, E., Petoukhov, M. V., Blackledge, M. & Svergun, D. I. Structural characterization of versatile proteins utilizing small-angle X-ray scattering. J. Am. Chem. Soc. 129, 5656–5664 (2007).
PubMed Google Scholar
Weber, B. et al. A single residue swap reveals rules of antibody area integrity. J. Biol. Chem. 293, 17107–17118 (2018).
CAS PubMed PubMed Central Google Scholar