key: cord-0881740-4pbaj6bx authors: Kudr, Jiri; Michalek, Petr; Ilieva, Lada; Adam, Vojtech; Zitka, Ondrej title: COVID-19: a challenge for electrochemical biosensors date: 2021-01-18 journal: Trends Analyt Chem DOI: 10.1016/j.trac.2021.116192 sha: 13907abf7237fb2f458372ca223f6e0f3ed5a101 doc_id: 881740 cord_uid: 4pbaj6bx Coronavirus disease (COVID-19) caused by SARS-CoV-2 has spread since the end of 2019 and has resulted in a pandemic with unprecedented socioeconomic consequences. This situation has created enormous demand for the improvement of current diagnostic methods and the development of new diagnostic methods for fast, low-cost and user-friendly confirmation of SARS-CoV-2 infection. This critical review focuses on viral electrochemical biosensors that are promising for the development of rapid medical COVID-19 diagnostic tools. The molecular biological properties of SARS-CoV-2 as well as currently known biochemical attributes of infection necessary for biosensor development are outlined. The advantages and drawbacks of conventional diagnostic methods, such as quantitative reverse-transcription polymerase chain reaction (qRT-PCR), are critically discussed. Electrochemical biosensors focusing on viral nucleic acid and whole viral particle detection are highlighted and discussed in detail. Finally, future perspectives on viral electrochemical biosensor development are briefly mentioned. The new coronavirus SARS-CoV-2 first emerged in December 2019 in Wuhan, Hubei Province, China 23 [1] . Due to its highly contagious nature, it has been rapidly spreading worldwide [2] . SARS-CoV-2 24 belongs to the order Nidovirales, family Coronaviridae, subfamily Orthocoronavirinae genus 25 Betacoronavirus and subgenus Sarbecovirus, which also include severe acute respiratory syndrome-26 related coronavirus (SARS-CoV) and Middle East respiratory syndrome-related coronavirus CoV) [3] [4] [5] . Virions of the Coronaviridae family are roughly spherical, 118-140 nm in diameter and 28 notable for the large spike (S) glycoprotein that extends from the virus envelope, which gave the name 29 to the whole family ( Fig. 1 ). [15] ). 114 115 The order Nidovirales contains positive-sense, single-stranded RNA (ssRNA) genomes that are 116 capped and polyadenylated. The Nidovirales order contains enveloped viruses with the largest RNA 117 genomes among currently known RNA viruses in the range of 12.7 to 33.5 kb, which can infect a variety of 118 vertebrate and invertebrate hosts [16, 17] . Unique among positive-sense ssRNA viruses, large 119 nidoviruses encode a 3′5′exoribonuclease (ExoN) that is implicated in controlling RNA replication 120 fidelity. Nidovirus genomes are typically organized into many ORFs occupying over 90% of the 121 genome. The products of these regions predominantly control genome expression, replication, virus 122 assembly and dissemination [16, 18] . 123 Most of the molecular diagnostics being developed for the diagnosis of COVID-19 infections involve 142 Undoubtedly, electrochemical biosensing of viruses is challenging and ambitious. However, 143 electrochemistry provides several well-known advances for biosensor design, such as inherent high 144 sensitivity, relatively low-cost sensors and equipment, user-friendly manipulation, fast analysis, and 145 suitability for miniaturization, hence creating POC devices. Current state-of-the-art electrochemical 146 biosensors and related technologies are critically discussed in subsequent paragraphs. CoV-2 spike glycoprotein (S protein) of the viral envelope. By binding to the S protein, these 179 antibodies prevent viral particles from interacting with cellular angiotensin-converting enzyme 2 180 (ACE2) receptors; hence, they are able to neutralize (neutralizing antibodies, nAbs) infection and 181 should help with vaccine design [40] . Such antibodies are suitable for the development of whole viral 182 particle biosensors since they focus on highly exposed parts of viral antigens 319 In this chapter, we will focus on practical examples of viral infection biosensors, which, in our 320 opinion, have demonstrated innovative and unique approaches. In this field, we have focused on only 321 biosensors of viral nucleic acids and whole viral particles, hence representing the only possibility for 322 early stage diagnostics and being suitable for the design of point-of-need devices (see Fig. 3 ). The first study we decided to mention is on Zika virus detection demonstrated by Lynch et al. [73] . 324 Zika virus is, as as along with SARS-CoV-2, a positive-sense ssRNA virus (Fig. 3a) In summary, the presented review summarizes current state-of-the-art approaches to viral 442 electrochemical biosensors, with a focus on SARS-CoV-2. We provide a brief overview of qRT-PCR 443 and serological tests, show their advantages and drawbacks and consider them regarding advances in 444 electrochemical tests. Individual parameters of electrochemical biosensors are critically discussed, 445 promising works are described and we provide future perspectives of the field. We expect that the 446 SARS-CoV-2 pandemic will accelerate the transformation of many analytical approaches from proof-447 of-concept status to applied technologies. 448 We demonstrate that electrochemistry brings several advantages among conventional SARS-CoV- A new coronavirus associated with human respiratory disease in China A pneumonia outbreak associated with a new 471 coronavirus of probable bat origin Structural and functional analysis of a potent 473 sarbecovirus neutralizing antibody Bat Coronaviruses in China Multivariate analyses of codon usage of SARS-CoV-2 and other betacoronaviruses Emerging SARS-CoV-2 mutation hot spots 477 include a novel RNA-dependent-RNA polymerase variant The establishment of reference sequence for SARS-CoV-2 and variation analysis INFECTIOUS DISEASES Genome analyses help track coronavirus' moves Multiplexing primer/probe sets for detection of SARS-CoV-2 by qRT-PCR Evaluating the accuracy of different respiratory specimens in the laboratory 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