Single-Molecule Analysis of SARS-CoV-2 Binding to C-Type Lectin Receptors
- PMID: 36758952
- PMCID: PMC9924085
- DOI: 10.1021/acs.nanolett.2c04931
Single-Molecule Analysis of SARS-CoV-2 Binding to C-Type Lectin Receptors
Abstract
Despite intense scrutiny throughout the pandemic, development of efficacious drugs against SARS-CoV-2 spread remains hindered. Understanding the underlying mechanisms of viral infection is fundamental for developing novel treatments. While angiotensin converting enzyme 2 (ACE2) is accepted as the key entry receptor of the virus, other infection mechanisms exist. Dendritic cell-specific intercellular adhesion molecule-3 grabbing non-integrin (DC-SIGN) and its counterpart DC-SIGN-related (DC-SIGNR, also known as L-SIGN) have been recognized as possessing functional roles in COVID-19 disease and binding to SARS-CoV-2 has been demonstrated previously with ensemble and qualitative techniques. Here we examine the thermodynamic and kinetic parameters of the ligand-receptor interaction between these C-type lectins and the SARS-CoV-2 S1 protein using force-distance curve-based AFM and biolayer interferometry. We evidence that the S1 receptor binding domain is likely involved in this bond formation. Further, we employed deglycosidases and examined a nonglycosylated S1 variant to confirm the significance of glycosylation in this interaction. We demonstrate that the high affinity interactions observed occur through a mechanism distinct from that of ACE2.
Keywords: DC-SIGN; L-SIGN; SARS-CoV-2; atomic force microscopy; kinetics; protein glycosylation; single molecule.
Conflict of interest statement
The authors declare no competing financial interest.
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References
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- Robinson P. C.; Liew D. F. L.; Tanner H. L.; Grainger J. R.; Dwek R. A.; Reisler R. B.; Steinman L.; Feldmann M.; Ho L.-P.; Hussell T.; Moss P.; Richards D.; Zitzmann N. COVID-19 Therapeutics: Challenges and Directions for the Future. Proc. Natl. Acad. Sci. U. S. A. 2022, 119 (15), e2119893119.10.1073/pnas.2119893119. - DOI - PMC - PubMed
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