## 1 Introduction  
The coronavirus disease of 2019 (COVID-19) is an emergent threat to human health worldwide. The emerging outbreak alarmed humans to quickly find a solution to stop it by developing molecular assays to detect the virus of COVID-19 in people. New quantitative real-time reverse-transcription PCR (RT-PCR) assays have been developed to diagnose COVID-19 by targeting two viral genome regions [1, 2]. Although the techniques above present high sensitivity and specificity, they have some limitations and challenges, such as their costs, robustness, sample preparation, and analysis time. Hence, there is a great demand for a new technique able to detect infection in the early stages. Surface-enhanced Raman spectroscopy (SERS) is a rapid, simple, less expensive, portable, and accurate method that can provide structural and chemical information about the virus via the fingerprint of its biomolecules [3, 4, 5]. SERS phenomena were observed and confirmed for the first time in 1970s on a roughened Ag metal surface, since this date, the detection sensitivity of Raman spectroscopy has significantly improved [6, 7]. SERS is a powerful vibrational spectroscopic technique that pushed the detection limit of structural and chemical sensing towards a single molecule [8, 9]. This ability is due to optical and chemical enhancement during the excitation of localized surface plasmon resonance (LSPR) into the interface of metal/air. LSPR can be enhanced and confined on tiny metallic nanostructures such as gold, silver, and palladium. The preferential use of gold in bioapplications is more given by its non-toxicity--e.g., in cell fingerprinting [10; 11; 12]. SERS offers a wide range of detection applications, either in a solution or a solid film. Since its appearance, SERS has shown strong capabilities for different applications in research and industries [13; 14]. The SERS technique was intensively used in several biological analyses, such as biological imaging [4; 5] and bacterial and viral detection [5; 15]. SARS-CoV-2 genomic RNA encodes two sets of proteins: nonstructural proteins, which act as complex replicase machinery, and structural proteins. The structural proteins represent the structural component of the mature virus and include: spike (S), envelope (E), membrane (M), and nucleocapsid (N) proteins. SARS-CoV-2 relies on spike protein (S) for penetrating host cells. The S protein subunit 1 (S1) binds to the human receptor angiotensin-converting enzyme 2 (ACE2) via the receptor-binding domain (RBD), while the S protein subunit 2 (S2) mediates the fusion to the host cell membrane [16]. Since the S protein is highly conserved [17], it is considered a promising target for discovering efficient antibodies, entry inhibitors, vaccines, and bio-detection approaches [18; 19; 20]. It has been shown that viral load varies by samples from a single patient. Temporal viral load profiles showed that salivary viral load was the highest among different samples and hit the peak during the first week after symptom onset and then declined [21]. Nowadays, using saliva samples can reduce the cost and time of specimen collection for SARS-CoV-2 detection. However, RT-PCR is a time-consuming technique (around three hours) and requires relatively expensive reagents and well-trained personnel. The properties, above, of the S protein pushed us to select it as a target for SERS detection. Recently, we have shown a modified approach using SERS to detect SARS-CoV-2 RBD. Fabricated silicon nanorods covered by Au/Ag nanostructures were used to achieve higher optical enhancement. The sensitivity of this approach hits nearly a single protein detection level of 1 pM [22]. In this work, we used our gold and silver deposited silicon nanorod substrates, successfully tested in our previous work [22]. A concentration-dependent SERS study carried out on the S protein confirmed the linear response property and sensitivity of the substrate and the transition in the conformational structures.