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Review
. 2021;13(1):18.
doi: 10.1007/s40820-020-00533-y. Epub 2020 Nov 2.

An Overview on SARS-CoV-2 (COVID-19) and Other Human Coronaviruses and Their Detection Capability via Amplification Assay, Chemical Sensing, Biosensing, Immunosensing, and Clinical Assays

Yasin Orooji #  1   2 , Hessamaddin Sohrabi #  3 , Nima Hemmat  4 , Fatemeh Oroojalian  5 , Behzad Baradaran  4 , Ahad Mokhtarzadeh  4 , Mohamad Mohaghegh  6 , Hassan Karimi-Maleh  7   8   9
Affiliations
Review

An Overview on SARS-CoV-2 (COVID-19) and Other Human Coronaviruses and Their Detection Capability via Amplification Assay, Chemical Sensing, Biosensing, Immunosensing, and Clinical Assays

Yasin Orooji et al. Nanomicro Lett. 2021.

Abstract

A novel coronavirus of zoonotic origin (SARS-CoV-2) has recently been recognized in patients with acute respiratory disease. COVID-19 causative agent is structurally and genetically similar to SARS and bat SARS-like coronaviruses. The drastic increase in the number of coronavirus and its genome sequence have given us an unprecedented opportunity to perform bioinformatics and genomics analysis on this class of viruses. Clinical tests like PCR and ELISA for rapid detection of this virus are urgently needed for early identification of infected patients. However, these techniques are expensive and not readily available for point-of-care (POC) applications. Currently, lack of any rapid, available, and reliable POC detection method gives rise to the progression of COVID-19 as a horrible global problem. To solve the negative features of clinical investigation, we provide a brief introduction of the general features of coronaviruses and describe various amplification assays, sensing, biosensing, immunosensing, and aptasensing for the determination of various groups of coronaviruses applied as a template for the detection of SARS-CoV-2. All sensing and biosensing techniques developed for the determination of various classes of coronaviruses are useful to recognize the newly immerged coronavirus, i.e., SARS-CoV-2. Also, the introduction of sensing and biosensing methods sheds light on the way of designing a proper screening system to detect the virus at the early stage of infection to tranquilize the speed and vastity of spreading. Among other approaches investigated among molecular approaches and PCR or recognition of viral diseases, LAMP-based methods and LFAs are of great importance for their numerous benefits, which can be helpful to design a universal platform for detection of future emerging pathogenic viruses.

Keywords: Amplification assay; Apta assay; ELISA; Sensing assay; qRT-PCR.

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Figures

Fig. 1
Fig. 1
Epidemic chart of confirmed COVID-19 up to August 23, 2020. Used with permission from Ref. [8]. Copyright 2020 World Health Organization
Fig. 2
Fig. 2
a Animal (natural and intermediate hosts) origin of human coronaviruses; b clinical presentation of patients with SARS-CoV-2 including common, uncommon, and severe symptoms of SARS-CoV-2. c Human coronavirus types: common human coronaviruses; 229E (alpha coronavirus), NL63 (alpha coronavirus), OC43 (beta coronavirus), HKU1 (beta coronavirus), and other human coronaviruses; MERS-CoV (the beta coronavirus that causes Middle East Respiratory Syndrome, or MERS), SARS-CoV (the beta coronavirus that causes the severe acute respiratory syndrome, or SARS), SARS-CoV-2 (the novel coronavirus that causes coronavirus disease 2019, or COVID-19); d diagram of coronavirus virion structure showing genome(ranges from 26 to 32 kilobases, the largest for an RNA virus) and structural proteins: spike (S), envelope (E), membrane (M), and nucleocapsid (N). N protein forms a complex with RNA and aids in the viral assembly after its replication; S, E, and M proteins create the viral envelope, and S protein is a club-shaped surface projection, giving the virus its characteristic crown-like appearance on electron microscopy, which is responsible for viral entry into the human cell
Fig. 3
Fig. 3
Schematic diagram showing the replication cycle of SARS-CoV-2. The virus moves into the target cells via an endosomal path. Initially, S protein connects to the cellular receptor angiotensin-converting enzyme 2 (ACE2) (1). The viral genome is set free (2) and decoded into viral replicase polyproteins pp1a and 1ab (3); then they are split into small products by viral proteinases (4). Sub-genomic negative-strand templates are created from intermittent transcript on the plus-strand genome and function as patterns for mRNA synthesis (5). The full-length negative-strand pattern is made as a pattern for genomic RNA (6). Viral nucleocapsids are accumulated from genomic RNA and N protein in the cytoplasm (7), followed by budding into the lumen (8), virions are then released from the cell through exocytosis (9)
Fig. 4
Fig. 4
Overview of different developed techniques for the detection of SARS-CoV-2
Fig. 5
Fig. 5
Overview of ELISA techniques for the detection of SARS-CoV-2
Fig. 6
Fig. 6
Based on the unsatisfactory efficiency of COVID-19 kits due to the detection lag of 7 and 14 days for appearing IgM and IgG in the serum of asymptomatic patients, porters would not be recognized, triggering the spread [–66]
Fig. 7
Fig. 7
a Immune-PCR, the immuno-PCR arrangement begins with a safe assay followed by PCR. Immuno-PCR is parallel to ELISA with the exception that terminal DNA is augmented by a PCR; b different immune-PCR platforms available, immuno-PCR, the sandwich setup of immuno-PCR, the direct setup of antigen detection, phage intermediated where single-chain variable fragments (scFv), magneto immuno-PCR, nanoparticle-amplified immune PCR. Redrawn from Ref Front Microbiol. 2019; 10: 1957 [67]
Fig. 8
Fig. 8
a Sensor chip for flexural plate wave. (1) Process of microfabrication with the help of technologies of microelectromechanical systems. (2) Top view image of flexural plate wave where the IDT period is equal to 200 µm along with 13 pairs and 1.6 µm is approximately considered for the total thickness. b Diagram of immobilization process represents the fact that an anti-SARS transfer to the sensor system with immobility by the hybrid protein of S-hACE2 can provide phase shifts because of utilizing hACE2 and including the protein S to the functionalized biosensor of flexural plate wave (FPW). c Control procedure of the FPW related to the combined minuscule arrangement for sensing and biosensing purposes. The FPW sensing framework system was constructed of a voltage follower, an FPW device, a Wien bridge oscillator (WBO), and a phase-locked loop (PLL) that consist of a phase detector (PD), low-pass filter (LPF) and voltage-controlled oscillator (VCO), a frequency phase detector, a liquid crystal display module (LCM) display, and a microprocessor. Adapted from Ref. (MCU) [86]
Fig. 9
Fig. 9
a Designing and b photograph of visual color alterations got from the recognition of 205 HPV, MTB, and MERS-CoV in the DNAcom presence. After acpcPNA addition, the yellow AgNPs turned red. The color also turned red because of AgNPs aggregation when the solution consists of the DNAnc and acpcPNA. On the other hand, altering the color from red (aggregation state) to yellow (non-aggregation state) in DNAcom presence, the intensity dependence on the DNA concentration is clear. c Selecting 100 nM MERS-CoV, MTB, and HPV recognition with the help of a multiplexed colorimetric sensor. Adapted from Ref. [87]. (Color figure online)
Fig. 10
Fig. 10
a Schematic presentation of immobilized Fn on the exterior part of an In2O3 nanowire FET apparatus device. The areas of Fn are highlighted in red with the plotted peptide sequence. Fn was connected to the related nanowires through the cysteine sulfhydryl group near the C-terminus, distant from the binding location. b Curves pertinent to a family of Ids–Vds and c a typical Ids–Vg curve (plotted both in logarithmic (blue)) and linear (red) achieved from one of our instruments functioning with the aqueous gate arrangement. Normalized electrical output (I/I0) versus time of a single functioning instrument. d–e Demonstrating the response curves to passivation upon the addition of consecutive aliquots of BSA. Upon increasing the BSA concentration (from pure 0.01* PBS), the baseline re-equilibrates at lower values of S-D current until stability is finally reached at 40 µM BSA, in 0.01* PBS. f Showing response for a nanowire device utilized with Fn. The red arrows show the times when the solution was increased to a specified concentration of N protein. The inset on the right side is the arrangement of our device through active sensing measurements. BSA protein was used to block sites for nonspecific binding. The Fn probe molecule was then used to specifically capture the target N protein. The inset on the left side is to show the plateau and the definition of response time. Adapted from Ref. [122]. (Color figure online)
Fig. 11
Fig. 11
AFM pictures of the consecutive binding of anti-SCVme on the gold-micropatterned surface and GBP-E-SCVme. a Bare Au surface, b immobilizing of the GBP-E-SCVme fusion proteins onto the gold surface, and c consequent connection of the anti-SCVme antibodies on the GBP-E-SCVme layer. Left, schematic of consecutive binding of GBP-E-SCVme and anti-SCVme on the gold micropatterns; middle, three-dimensional topological images; right, the cross-sectional contours of samples a–c, sequentially (these are average height differences of the individual scan lines from each area). d SPR sensorgrams for (1) sensitive and (2) selective recognition of anti-SCVme utilizing the GBP-E-SCVme-imbedded gold sensor chip at different concentrations (0.1, 1, 10, 50, and 100 µg mL−1) of anti-SCVme and (1 and 10 µg mL−1) of mouse IgG as negative controls. SPRi analysis of the sequential binding of GBP-E-SCVme and anti-SCVme onto gold micropatterns composed of 50-nm-diameter circles. e Three-dimensional and two-dimensional (inset) images of bare gold micropatterns as controls (sample (i)); binding of GBP-E-SCVme fusion proteins onto the gold patterns (sample (ii)); and successive binding of GBP-E-SCVme and anti-SCVme onto the gold patterns (sample (iii)). Spot intensities of the three samples shown in scanned images were measured through the gold circle micropatterns. Adapted from Ref. [123]
Fig. 12
Fig. 12
Schematic explanation of quick SARS-CoV-2 IgM–IgG combined antibody test. a Schematic of the recognition device. b An explanation of various experimental consequences. c Relates to the control line, G means IgG line, M pertinent to IgM line. Illustrative photograph for various patient blood experimental consequences. #13 shows both IgG and IgM positive, #14 shows IgM weak positive, #15 illustrate both IgG and IgM negative, #16) IgG weak positive, #17) IgG positive, #18) IgM positive. (Redrawn from Ref. [133])
Fig. 13
Fig. 13
Scheme demonstrating the MERS-CoV immunosensor preparation and also the recognition procedure. The biosensor comprises a competitive immunoassay carried out on DEP array electrodes nanostructured with gold nanoparticles to allow the multiplexed recognition of various CoV. a Immunosensor array chip for coronavirus. b Stages of immunosensor construction. c Recognition procedure of competitive immunosensor for the virus. Redrawn from Ref. [146]
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References

    1. Drosten C, Gunther S, Preiser W, van der Werf S, Brodt HR, et al. Identification of a novel coronavirus in patients with severe acute respiratory syndrome. N. Engl. J. Med. 2003;348(20):1967–1976. doi: 10.1056/NEJMoa030747. - DOI - PubMed
    1. Keogh-Brown MR, Smith RD. The economic impact of SARS: How does the reality match the predictions? Health Policy. 2008;88(1):110–120. doi: 10.1016/j.healthpol.2008.03.003. - DOI - PMC - PubMed
    1. de Groot RJ, Baker SC, Baric RS, Brown CS, Drosten C, et al. Commentary: middle east respiratory syndrome coronavirus (MERS-CoV): announcement of the coronavirus study group. J. Virol. 2013;87(14):7790–7792. doi: 10.1128/JVI.01244-13. - DOI - PMC - PubMed
    1. Zaki AM, van Boheemen S, Bestebroer TM, Osterhaus AD, Fouchier RA. Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia. N. Engl. J. Med. 2012;367(19):1814–1820. doi: 10.1056/NEJMoa1211721. - DOI - PubMed
    1. Wong ACP, Li X, Lau SKP, Woo PCY. Global epidemiology of bat coronaviruses. Viruses. 2019;11(2):174. doi: 10.3390/v11020174. - DOI - PMC - PubMed

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