Various signal determination methods can be applied in the design of MIP-based sensors, but mostly potentiodynamic electrochemical techniques [113] or QCM-based [100,117] approaches are used for this purpose. Development and application of MIPs in sensor design is reasonable because MIPs can be developed for small and low molecular weight molecules [75,118]. sometimes enable label-free detection of an analyte. Along with the specification of biosensors, we also provide a brief overview of generally used testing techniques, and the description of Naproxen sodium the structure, life cycle and immune host response to SARS-CoV-2, and some deeper details of analytical signal detection principles. Keywords: COVID-19, SARS-CoV-2 virus, RNA analysis, bioelectrochemistry, biosensors, electrochemical immunosensors, antigen-antibody interaction, immune complex, molecularly imprinted polymers (MIPs), surface modification by immobilization of biomolecules 1. Introduction The spreading of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is causing coronavirus disease 2019 (COVID-19) was declared as a global pandemic in March 2020. The main threat of the Naproxen sodium pandemic is the overloading of the health systems. The AMH key tool against infection spreading is decreasing its distribution rate, in particular by monitoring the infected people and their contacts. For the Naproxen sodium successful control, the primary step is the detection of SARS-CoV-2 in an organism. Hence, the development and introduction of rapid, precise, and sensitive detection methods are required. For a better understanding of the existing detection method principles, it is worth dwelling in more detail on the structure of SARS-CoV-2, its life cycle and the induced host response. 2. The Structure of SARS-CoV-2 Virus The coronavirus SARS-CoV-2 is a spherical structure with a diameter of about 130 nm [1,2,3], its surface is riddled by spikes making the viral particle look like the Suns corona, therefore, similarly looking viruses are named as coronaviruses. Inside the viral structure, a helically symmetrical nucleocapsid containing ssRNA, which is a genetic information carrier of this virus, is located. The SARS-CoV-2 has a typical for the coronaviruses (CoVs) genome, which is by about 80% and 50% similar to that of known SARS-CoV and middle east respiratory syndrome coronavirus (MERS-CoV), respectively [4]. The genome is including no less than ten open reading frames (ORFs). The virus replicase-transcriptase complex, which is formed by two large polyproteins, is encoded on the 5-terminal two-thirds of the genome ORF1a/b, while the entire part of the genome encodes four key structural proteins, that are, spike (S), envelope (E), nucleocapsid (N) and membrane (M) proteins (Table 1). These proteins play a crucial role, primarily in the formation of viral particles, and are taking part in other stages of the SARS-CoV-2 life cycle [4]. The S-protein, a large transmembrane homo-trimer (150 kDa), which consists of two subunits, namely, S1 and S2 [4,5,6] and is responsible for the virus attaching to a host cell, followed by fusion and infection [7,8]. An attachment to a host receptor performs through the receptor-binding domain (RBD) in the S1 subunit and then fusion of the viral and host membranes takes place through the S2 subunit [9,10,11,12]. The E-protein (8C12 kDa) is a transmembrane and also the smallest one. The smaller part of the E-protein, which is expressed in the infected host cells, is forming the viral overall envelope, while the larger part of this protein is involved in viral association and maturation [13,14]. The N-protein is bound with viral ssRNA, and it is responsible for virion formation [15]. The N-protein consists Naproxen sodium of a monomeric N-terminal domain (NTD) with a mass value of about 15.4 kDa, and a dimeric C-terminal domain (CTD) with a mass of ~28.7 kDa, in such a way that both are needed for the ssRNA binding [15,16,17]. The M-protein (25C30 kDa) is responsible for the shaping of the viral envelope [18]. The M-protein is characterized by the cooperation with 3 other main proteins of SARS-CoV-2. The interaction Naproxen sodium between S- and M-proteins helps to hold the S-protein in the endoplasmic reticulum (ER)-Golgi intermediate compartment (ERGIC)/Golgi complex followed by its integration into novel virions [19]. The interplay of M- and N-proteins leads to the stabilization of the N-protein/ssRNA complex (nucleocapsid) and the internal core of virions [20]. The complex of M- and E-proteins is involved in the process of.