Understanding the Excitation Wavelength Dependence and Thermal Stability of the SARS-CoV-2 Receptor-Binding Domain Using Surface-Enhanced Raman Scattering and Machine Learning

Kunyan Zhang; Ziyang Wang; He Liu; Néstor Perea-López; Jeewan C Ranasinghe; George Bepete; Allen M Minns; Randall M Rossi; Scott E Lindner; Sharon X Huang; Mauricio Terrones; Shengxi Huang

doi:10.1021/acsphotonics.2c00456

Understanding the Excitation Wavelength Dependence and Thermal Stability of the SARS-CoV-2 Receptor-Binding Domain Using Surface-Enhanced Raman Scattering and Machine Learning

ACS Photonics. 2022 Aug 25;9(9):2963-2972. doi: 10.1021/acsphotonics.2c00456. eCollection 2022 Sep 21.

Authors

Kunyan Zhang¹, Ziyang Wang^{1

2}, He Liu³, Néstor Perea-López^{4

5}, Jeewan C Ranasinghe^{1

2}, George Bepete^{3

4

5}, Allen M Minns^{6

7}, Randall M Rossi⁷, Scott E Lindner^{6

7}, Sharon X Huang⁸, Mauricio Terrones^{3

4

5

9

10}, Shengxi Huang^{1

2}

Affiliations

¹ Department of Electrical Engineering, The Pennsylvania State University, University Park, Pennsylvania16802, United States.
² Department of Electrical and Computer Engineering, Rice University, Houston, Texas77005, United States.
³ Department of Chemistry, The Pennsylvania State University, University Park, Pennsylvania16802, United States.
⁴ Department of Physics, The Pennsylvania State University, University Park, Pennsylvania16802, United States.
⁵ Center for 2-Dimensional and Layered Materials, The Pennsylvania State University, University Park, Pennsylvania16802, United States.
⁶ Department of Biochemistry and Molecular Biology, Center for Infectious Disease Dynamics, The Pennsylvania State University, University Park, Pennsylvania16802, United States.
⁷ Huck Institutes of the Life Sciences, The Pennsylvania State University, University Park, Pennsylvania16802, United States.
⁸ College of Information Sciences and Technology, The Pennsylvania State University, University Park, Pennsylvania16802, United States.
⁹ Department of Materials Science and Engineering, The Pennsylvania State University, University Park, Pennsylvania16802, United States.
¹⁰ Research Initiative for Supra Materials, Shinshu University, 4-17-1 Wakasato, Nagano380-8553, Japan.

PMID: 37552735
DOI: 10.1021/acsphotonics.2c00456

Abstract

COVID-19 has cost millions of lives worldwide. The constant mutation of SARS-CoV-2 calls for thorough research to facilitate the development of variant surveillance. In this work, we studied the fundamental properties related to the optical identification of the receptor-binding domain (RBD) of SARS-CoV-2 spike protein, a key component of viral infection. The Raman modes of the SARS-CoV-2 RBD were captured by surface-enhanced Raman spectroscopy (SERS) using gold nanoparticles (AuNPs). The observed Raman enhancement strongly depends on the excitation wavelength as a result of the aggregation of AuNPs. The characteristic Raman spectra of RBDs from SARS-CoV-2 and MERS-CoV were analyzed by principal component analysis that reveals the role of secondary structures in the SERS process, which is corroborated with the thermal stability under laser heating. We can easily distinguish the Raman spectra of two RBDs using machine learning algorithms with accuracy, precision, recall, and F₁ scores all over 95%. Our work provides an in-depth understanding of the SARS-CoV-2 RBD and paves the way toward rapid analysis and discrimination of complex proteins of infectious viruses and other biomolecules.