key: cord-337220-yv7qdvzi
authors: Demeke, Addis; Samaddar, Manalee; Alharbi, Mona G.; Al-Hindi, Rashad R.; Bhunia, Arun K.
title: Biosensor and molecular-based methods for the detection of human coronaviruses: A review
date: 2020-09-08
journal: Mol Cell Probes
DOI: 10.1016/j.mcp.2020.101662
sha: 
doc_id: 337220
cord_uid: yv7qdvzi

The ongoing crisis due to the global pandemic caused by a highly contagious coronavirus (Coronavirus disease – 2019; COVID-19) and the lack of either proven effective therapy or a vaccine has made diagnostic a valuable tool in disease tracking and prevention. The complex nature of this newly emerging virus calls for scientists’ attention to find the most reliable, highly sensitive, and selective detection techniques for better control or spread of the disease. Reverse transcriptase-polymerase chain reaction (RT-PCR) and serology-based tests are currently being used. However, the speed and accuracy of these tests may not meet the current demand; thus, alternative technology platforms are being developed. Nano biosensor technology platforms have been established as a promising diagnostic tool for rapid and accurate detection of viruses as well as other life-threatening diseases even in resource-limited settings. This review aims to provide a short overview of recent advancements in molecular and biosensor-based diagnosis of viruses, including the human coronaviruses, and highlight the challenges and future perspectives of these detection technologies.

Another reverse transcription loop-mediated isothermal amplification (RT-LAMP) was 126 developed to detect the ORF1ab and S genes of SARS-CoV-2 in 18 to 20 min. In this point-of-127 care testing platform, positive results could be judged by the naked eye with a color change from 128 orange to green [19] . DNA Endonuclease-Targeted CRISPR Trans Reporter (DETECTR) is a 129 comparatively new method of SARS-Cov-2 detection [20] . This assay involves simultaneous 130 reverse transcription and isothermal amplification using loop-mediated amplification (RT-131 LAMP) for RNA, followed by Cas12 detection of predefined coronavirus sequences, after which 132 cleavage of a reporter molecule confirms detection of the E and N genes of SARS-CoV-2. Cas12 133 fluorescent signals can be visualized by lateral flow assay within 5 min [21] . 134

Serological tests can play a critical role in the fight against COVID-19 by helping 136 healthcare professionals to identify individuals who have overcome infection in the past and 137 have developed an immune response. COVID-19 disease is reported to induce acute antibody 138 (IgM, IgG) response in all patients and the levels of anti-viral antibodies are plateaued within 6-139 days after seroconversion [22] . Therefore, a "serology" test can be performed to measure anti-140 viral antibodies in the blood and can potentially be used in patients with negative RT-PCR or 141 asymptomatic patients [23] . Serological/antibody-based assays are rapid and efficient for the 142 screening of many pathogenic infections, as pathogen-specific IgM and IgG antibodies can be 143 detected with various immunoassays [24] , which has relatively high throughput capacity and less 144 stringent specimen requirements (uniformity in serum collection) than viral RNA-based assays 145 [14] . Detecting IgM and IgG against the SERS-CoV-2 offers an alternate means to diagnose a 146 patient. Rapid lateral flow-based assays for anti-COVID-19 antibodies (IgM and IgG) are under 147 development which will play an important role in the epidemiological investigation of the 148 disease [9] . This method can be used to quickly screen all febrile patients effectively, as large-149 scale confirmation or exclusion of patients is essential for preventing the spread of disease and 150 for an epidemiological survey. However, there is a concern if the serology test could be useful 151 for the diagnosis of asymptomatic or symptomatic patients who may not mount a detectable 152 immune response. Interestingly, anti-SARS-CoV-2 antibodies (seroconversion requires at least 7 153 days of infection in a patient) have the potentials to neutralize the virus and to protect people 154 from developing future infections [25] . Therefore, the convalescent plasma has been used as 155 therapy for the treatment of critically ill COVID-19 patients [26, 27] The biosensor was developed by using a spike protein of SARS-CoV-2 immobilized onto the 237 FET graphene sheet (a two-dimensional sheet of hexagonal oriented carbon atom) with 1-pyrene 238 butyric acid N-hydroxy succinimide ester (PBASE) (Figure 1) . The team used the spike protein 239 of the virus due to its sequence diversity among the coronaviruses and they have evaluated its 240 performance by enzyme-linked immunosorbent assay (ELISA) before immobilizing onto the 241 FET surface. The sensor was designed to detect the SARS-CoV-2 virus in clinical samples with a 242 1 fg/mL detection limit. Most importantly, the device showed no significant cross-reactivity with 243 the MERS-CoV antigen. Hence, the sensor developed by this research group provides fast, 244 highly sensitive, and specific detection of the SARS-CoV-2 virus in clinical samples. 245 Disease caused by coronaviruses became the major public health threat worldwide [1]. It 359 is highly contagious thus there is a great demand for diagnostic/detection tool that is rapid, 360 accurate, user-friendly to support the healthcare industry. RT-PCR has been the key diagnostic 361 tool to combat the COVD-19 pandemic and is considered a major diagnostic tool for several 362 other viral diseases. However, this method is labor-intensive and often requires several days to 363 obtain results, which is counter-productive for tracing/tracking since the SARS-CoV-2 spreads 364 rapidly. The application of nano biosensors (using nanoparticles and nanomaterials) has the 365 potential to deliver results quickly with high accuracy. However, biosensors may encounter 366 many challenges in the clinical settings, such as biofouling which restricts the widespread 367 utilization of biosensors [107] . It has been investigated that the durability or functionality of 368 immobilized sensors is diminished by particle buildup i.e., biofouling can considerably impede 369 the influx of analyte to the detector. Another challenge is that some of the immunosensors are 

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