## 4 Conclusions  
For the first time, we reported a swift detection method of COVID-19 proteins in saliva at a very low concentration during 3 s and by using an ultra-low power. A SERS substrate containing silver/gold nanoparticles, covered a silicon wire and exhibited high optical enhancement for this detection. We were able to identify the S and RBD proteins from saliva without any purification or removal of debris at a very low concentration of \(10^{-9}\) M. Statistical studies showed a good separation between the proteins in saliva by taking different positions on the surface of the substrate. In order to validate the selectivity of our SERS substrate, we successfully identified a protein such as the BSA in the saliva sample (where other proteins are present). Our results was supported by a finite element simulation method in order to evaluate the extent and order of magnitude of optical enhancement, and the effect of the bio-medium refractive index on the plasmon resonance shift. Finally, this comparative study between S and RBD proteins, in the presence of a complex medium such as saliva, provides more insight and knowledge to the biosensing communities, in order to develop an automated recognition tool to detect viral proteins.  
**Supplementary Materials:** The following supporting information can be downloaded at: [[https://www.mdpi.com/article/10.3390/app12105039/s1](https://www.mdpi.com/article/10.3390/app12105039/s1)]([https://www.mdpi.com/article/10.3390/app12105039/s1](https://www.mdpi.com/article/10.3390/app12105039/s1)), Figure S1. SERS spectra of (a) Saliva +S (SLS) and (b) Saliva (SL) without any treatment; Figure S2. SERS spectra of (a) Saliva +RBD (SLR) and (b) Saliva (SL) without any treatment; Figure S3. SERS spectra of (a) Saliva +BSA (SL-BSA) and (b) Saliva (SL) without any treatment.  
**Author Contributions:** Conceptualization, M.B.A., C.D. and C.A.; Data curation, M.B.A., C.D., A.A. ([PERSON]) and C.A.; Formal analysis, M.B.A., C.D., M.A., A.A. ([PERSON]), A.A. ([PERSON]) and C.A.; Funding acquisition, C.A.; Investigation, M.B.A., C.D., M.A., A.A. ([PERSON]), A.A. ([PERSON]) and C.A.; Methodology, M.B.A., C.D. and C.A.; Project administration, C.A.; Resources, M.B.A., M.A., A.A. ([PERSON]), A.A. ([PERSON]) and C.A.; Software, C.D. and C.A.; Supervision, C.A.; Validation, M.B.A., C.D and C.A.; Visualization, M.B.A., A.A. ([PERSON]) and C.A.; Writing--original draft, C.A.; Writing--review & editing, M.B.A., C.D., M.A., A.A. ([PERSON]), A.A. ([PERSON]) and C.A. All authors have read and agreed to the published version of the manuscript.  
**Funding:** This research was funded by the Deanship of Scientific Research, Vice Presidency for Graduate Studies and Scientific Research, King Faisal University, Saudi Arabia, grant number GRANT358 and the APC was funded by the Deanship of Scientific Research, Vice Presidency for Graduate Studies and Scientific Research, King Faisal University, Saudi Arabia.  
**Institutional Review Board Statement:** Not applicable.  
**Informed Consent Statement:** Not applicable.  
**Data Availability Statement:** Not applicable.  
**Acknowledgments:** This work was supported by the Deanship of Scientific Research, Vice Presidency for Graduate Studies and Scientific Research, King Faisal University, Saudi Arabia [Project No.GRANT358].  
**Conflicts of Interest:** The authors declare no conflict of interest.