A Review on SERS-Based Detection of Human Virus Infections: Influenza and Coronavirus

Abstract

The diagnosis of respiratory viruses of zoonotic origin (RVsZO) such as influenza and coronaviruses in humans is crucial, because their spread and pandemic threat are the highest. Surface-enhanced Raman spectroscopy (SERS) is an analytical technique with promising impact for the point-of-care diagnosis of viruses. It has been applied to a variety of influenza A virus subtypes, such as the H1N1 and the novel coronavirus SARS-CoV-2. In this work, a review of the strategies used for the detection of RVsZO by SERS is presented. In addition, relevant information about the SERS technique, anthropozoonosis, and RVsZO is provided for a better understanding of the theme. The direct identification is based on trapping the viruses within the interstices of plasmonic nanoparticles and recording the SERS signal from gene fragments or membrane proteins. Quantitative mono- and multiplexed assays have been achieved following an indirect format through a SERS-based sandwich immunoassay. Based on this review, the development of multiplex assays that incorporate the detection of RVsZO together with their specific biomarkers and/or secondary disease biomarkers resulting from the infection progress would be desirable. These configurations could be used as a double confirmation or to evaluate the health condition of the patient.

Keywords: COVID-19; SERS; anthropozoonosis; coronavirus; influenza; quantification strategies; virus; zoonosis.

Figure 1

Schematic representation of the surface-enhanced Raman scattering (SERS) from the electromagnetic (EM) effect.

Figure 2

Timeline of zoonotic viruses from 1757 to the present day [46,47,48,49,50,51,52,53,54,55,56,57,58].

Figure 3

Scheme of the paths involved in the occurrence of an anthropozoonosis: (a) direct and (b) indirect infections.

Figure 4

Scheme of the avian influenza virus.

Figure 5

Operating procedure scheme of: (a) the immunoassay with protein G. Adapted with permission from ref. [93]. Copyright 2016 the Royal Society of Chemistry. (b) Functional nanoparticles system. Reproduced with permission from ref. [94]. Copyright 2019 American Chemical Society. (c) SERS-based lateral flow immunoassay strip. Reproduced with permission from ref. [95]. Copyright 2019 American Chemical Society.

Figure 6

Scheme of the avian influenza H7N9.

Figure 7

Surface-enhanced Raman scattering-based lateral flow immunoassay strips (SERS-LFIAS). Adapted with permission from ref. [106]. Copyright 2019 Elsevier Science S.A.

Figure 8

SERS quantification of the H7N9 virus, including the amplification process of the H7 and N9 gene fragments via reaction with exonuclease III. MCH: mercaptohexanol added to avoid nonspecific adsorption. Reproduced with permission from ref. [111]. Copyright 2019 Elsevier Science S.A.

Figure 9

Schematic illustration of the SERS-based magnetic immunoassay for H3N2 virus detection. AIV: Type A influenza virus. Adapted with permission from ref. [119]. Copyright 2017 Elsevier Science S.A.

Figure 10

Scheme of the sandwich-like aptasensor for influenza virus detection. Steps: (1) immobilization of the aptamer onto Ag nanoparticles, (2) capture of the virus on the SERS substrate, and (3) interaction of the reporter molecule–aptamer complex with the virus. Adapted from ref [120].

Figure 11

Representation of the steps to obtain the SERS tag-functionalized immunocomplex on which the SERS signal was recorded for the detection of the H5N1 virus. IMC-MB: immunocomplex on magnetic beads.

Figure 12

Scheme of the coronavirus structure.

Figure 13

Cumulative confirmed cases and deaths related to the COVID-19 disease [173].

Figure 14

Representation of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus recognition by the ACE-2 enzyme, before its entry into the cell.

Figure 15

Scheme of the analytical strategy for the diagnosis of SARS-CoV-2 by SERS through the recognition of their spike protein receptor-binding domain (RBD) by the ACE-2 protein. The response of the analytical system in the presence of a free spike protein is also shown [194].