1. Zhou, P. et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 579, 270–273. https://doi. org/10.1038/s41586-020-2012-7 (2020).
2. Walls, A. C. et al. Structure, function, and antigenicity of the SARS-CoV-2 spike glycoprotein. Cell 181, 281–292. https://doi.org/ 10.1016/j.cell.2020.02.058 (2020).
3. Hoffmann, M. et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibi- tor. Cell 181, 271–280. https://doi.org/10.1016/j.cell.2020.02.052 (2020).
4. Yan, R. et al. Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2. Science 367, 1444–1448. https://doi. org/10.1126/science.abb2762 (2020).
5. Lan, J. et al. Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor. Nature 581, 215–220. https://doi.org/10.1038/s41586-020-2180-5 (2020).
6. Li, W. et al. Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature 426, 450–454. https://doi. org/10.1038/nature02145 (2003).
7. Lu, R. et al. Genomic characterisation and epidemiology of 2019 novel coronavirus: Implications for virus origins and receptor binding. Lancet 395, 565–574. https://doi.org/10.1016/S0140-6736(20)30251-8 (2020).
8. Drozdzal, S. et al. FDA approved drugs with pharmacotherapeutic potential for SARS-CoV-2 (COVID-19) therapy. Drug Resist. Update 53, 100719. https://doi.org/10.1016/j.drup.2020.100719 (2020).
9. Artese, A. et al. Current status of antivirals and druggable targets of SARS CoV-2 and other human pathogenic coronaviruses. Drug Resist. Update 53, 100721. https://doi.org/10.1016/j.drup.2020.100721 (2020).
10. Baum, A. et al. REGN-COV2 antibodies prevent and treat SARS-CoV-2 infection in rhesus macaques and hamsters. Science 370, 1110–1115. https://doi.org/10.1126/science.abe2402 (2020).
11. Jiang, S., Hillyer, C. & Du, L. Neutralizing antibodies against SARS-CoV-2 and other human coronaviruses. Trends Immunol. 41, 355–359. https://doi.org/10.1016/j.it.2020.03.007 (2020).
12. Oliviero, A., de Castro, F., Coperchini, F., Chiovato, L. & Rotondi, M. COVID-19 pulmonary and olfactory dysfunctions: Is the chemokine CXCL10 the common denominator?. Neuroscientist https://doi.org/10.1177/1073858420939033 (2020).
13. Wu, Y. et al. Identification of human single-domain antibodies against SARS-CoV-2. Cell Host Microbe 27, 891–898. https://doi. org/10.1016/j.chom.2020.04.023 (2020).
14. Huo, J. et al. Neutralizing nanobodies bind SARS-CoV-2 spike RBD and block interaction with ACE2. Nat. Struct. Mol. Biol. 27, 846–854. https://doi.org/10.1038/s41594-020-0469-6 (2020).
15. Barnes, C. O. et al. SARS-CoV-2 neutralizing antibody structures inform therapeutic strategies. Nature 588, 682–687. https://doi. org/10.1038/s41586-020-2852-1 (2020).
16. Hansen, J. et al. Studies in humanized mice and convalescent humans yield a SARS-CoV-2 antibody cocktail. Science 369, 1010– 1014. https://doi.org/10.1126/science.abd0827 (2020).
17. Monteil, V. et al. Inhibition of SARS-CoV-2 infections in engineered human tissues using clinical-grade soluble human ACE2. Cell 181, 905–913. https://doi.org/10.1016/j.cell.2020.04.004 (2020).
18. Cardone, M., Yano, M., Rosenberg, A. S. & Puig, M. Lessons learned to date on COVID-19 hyperinflammatory syndrome: Con- siderations for interventions to mitigate SARS-CoV-2 viral infection and detrimental hyperinflammation. Front. Immunol. 11, 1131. https://doi.org/10.3389/fimmu.2020.01131 (2020).
19. Iwanaga, N. et al. Novel ACE2-IgG1 fusions with improved activity against SARS-CoV2. bioRxiv https://doi.org/10.1101/2020.06. 15.152157 (2020).
20. Abe, R. et al. “Quenchbodies”: Quench-based antibody probes that show antigen-dependent fluorescence. J. Am. Chem. Soc. 133, 17386–17394. https://doi.org/10.1021/ja205925j (2011).
21. Abe, R. et al. Ultra Q-bodies: Quench-based antibody probes that utilize dye-dye interactions with enhanced antigen-dependent fluorescence. Sci. Rep. 4, 4640. https://doi.org/10.1038/srep04640 (2014).
22. Ohashi, H. et al. Insight into the working mechanism of quenchbody: Transition of the dye around antibody variable region that fluoresces upon antigen binding. Bioconjug. Chem. 27, 2248–2253 (2016).
23. Zhao, S., Dong, J., Jeong, H. J., Okumura, K. & Ueda, H. Rapid detection of the neonicotinoid insecticide imidacloprid using a quenchbody assay. Anal. Bioanal. Chem. 410, 4219–4226. https://doi.org/10.1007/s00216-018-1074-y (2018).
24. Inoue, A., Ohmuro-Matsuyama, Y., Kitaguchi, T. & Ueda, H. Creation of a nanobody-based fluorescent immunosensor mini Q-body for rapid signal-on detection of small hapten methotrexate. ACS Sens. 5, 3457–3464. https://doi.org/10.1021/acssensors. 0c01404 (2020).
25. Dong, J., Fujita, R., Zako, T. & Ueda, H. Construction of Quenchbodies to detect and image amyloid beta oligomers. Anal. Biochem. 550, 61–67. https://doi.org/10.1016/j.ab.2018.04.016 (2018).
26. Jeong, H. J. et al. Development of a quenchbody for the detection and imaging of the cancer-related tight-junction-associated membrane protein Claudin. Anal. Chem. 89, 10783–10789. https://doi.org/10.1021/acs.analchem.7b02047 (2017).
27. Jeong, H. J., Dong, J. & Ueda, H. Single-step detection of the influenza virus hemagglutinin using bacterially-produced Quench- bodies. Sensors 19, 52. https://doi.org/10.3390/s19010052 (2018).
28. Dong, J., Oka, Y., Jeong, H. J., Ohmuro-Matsuyama, Y. & Ueda, H. Detection and destruction of HER2-positive cancer cells by Ultra Quenchbody-siRNA complex. Biotechnol. Bioeng. 117, 1259–1269. https://doi.org/10.1002/bit.27302 (2020).
29. Jeong, H. J. et al. Detection of vimentin serine phosphorylation by multicolor Quenchbodies. Biosens. Bioelectron. 40, 17–23. https://doi.org/10.1016/j.bios.2012.06.030 (2013).
30. Dong, J., Jeong, H. J. & Ueda, H. Preparation of Quenchbodies by protein transamination reaction. J. Biosci. Bioeng. 122, 125–130. https://doi.org/10.1016/j.jbiosc.2015.12.010 (2016).
31. Jeong, H. J. et al. Construction of dye-stapled Quenchbodies by photochemical crosslinking to antibody nucleotide-binding sites. Chem. Commun. (Camb.) 53, 10200–10203. https://doi.org/10.1039/c7cc03043f (2017).
32. Dong, J. et al. PM Q-probe: A fluorescent binding protein that converts many antibodies to a fluorescent biosensor. Biosens. Bio- electron. 165, 112425. https://doi.org/10.1016/j.bios.2020.112425 (2020).
33. Smith, G. P. Filamentous fusion phage: Novel expression vectors that display cloned antigens on the virion surface. Science 228, 1315–1317. https://doi.org/10.1126/science.4001944 (1985).
34. McCafferty, J., Griffiths, A. D., Winter, G. & Chiswell, D. J. Phage antibodies: Filamentous phage displaying antibody variable domains. Nature 348, 552–554. https://doi.org/10.1038/348552a0 (1990).
35. de Wildt, R. M. T., Mundy, C. R., Gorick, B. D. & Tomlinson, I. M. Antibody arrays for high-throughput screening of antibody– antigen interactions. Nat. Biotechnol. 18, 989–994. https://doi.org/10.1038/79494 (2000).
36. Swindells, M. B. et al. abYsis: Integrated antibody sequence and structure: Management, analysis and prediction. J. Mol. Biol. 429, 356–364 (2017).
37. Parray, H. A. et al. Identification of an anti-SARS-CoV-2 receptor-binding domain-directed human monoclonal antibody from a naive semisynthetic library. J. Biol. Chem. 295, 12814–12821. https://doi.org/10.1074/jbc.AC120.014918 (2020).
38. Yuan, M. et al. Identification and characterization of a monoclonal antibody blocking the SARS-CoV-2 spike protein-ACE2 interaction. Cell Mol. Immunol. 18, 1562–1564. https://doi.org/10.1038/s41423-021-00684-x (2021).
39. Quijano-Rubio, A. et al. De novo design of modular and tunable protein biosensors. Nature 591, 482–487. https://doi.org/10.1038/ s41586-021-03258-z (2021).
40. Grant, B. D. et al. SARS-CoV-2 coronavirus nucleocapsid antigen-detecting half-strip lateral flow assay toward the development of point of care tests using commercially available reagents. Anal. Chem. 92, 11305–11309. https://doi.org/10.1021/acs.analchem. 0c01975 (2020).
41. Pollock, N. R. et al. Correlation of SARS-CoV-2 nucleocapsid antigen and RNA concentrations in nasopharyngeal samples from children and adults using an ultrasensitive and quantitative antigen assay. J. Clin. Microbiol. 59, e03077. https://doi.org/10.1128/ JCM.03077-20 (2021).
42. Shan, D. et al. N-protein presents early in blood, dried blood and saliva during asymptomatic and symptomatic SARS-CoV-2 infection. Nat. Commun. 12, 1931. https://doi.org/10.1038/s41467-021-22072-9 (2021).
43. Laemmli, U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227, 680–685. https:// doi.org/10.1038/227680a0 (1970).
44. Pack, P., Müller, K., Zahn, R. & Plückthun, A. Tetravalent miniantibodies with high avidity assembling in Escherichia coli. J. Mol. Biol. 246, 28–34. https://doi.org/10.1006/jmbi.1994.0062 (1995).