Development of a SARS-CoV-2-derived receptor-binding domain-based ACE2 biosensor

Suh, Jung-Soo; Kim, Heon-Su; Kim, Tae-Jin

doi:10.1016/j.snb.2021.129663

Cited by 17 publications

(9 citation statements)

References 39 publications

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“…The heterogeneous virus then infects target cells through ACE2. Since ACE2 is the main doorway for SARS-CoV-2 variants, ,− employing this receptor for biosensor development can be an effective screening strategy for variants. ,− We introduced a synthetic virus, which we used to successfully develop and validate a virus-receptor-based biosensor. Our results showed that ACE2 can be a useful recognition element for developing highly sensitive biosensors to SARS-CoV-2 variants.…”

Section: Resultsmentioning

confidence: 99%

SARS-CoV-2 Variant Screening Using a Virus-Receptor-Based Electrical Biosensor

et al. 2021

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SARS-CoV-2 variants are of particular interest because they can potentially increase the transmissibility and virulence of COVID-19 or reduce the effectiveness of available vaccines. However, screening SARS-CoV-2 variants is a challenge because biosensors target viral components that can mutate. One promising strategy is to screen variants via angiotensin-converting enzyme 2 (ACE2), a virus receptor shared by all known SARS-CoV-2 variants. Here we designed a highly sensitive and portable COVID-19 screening biosensor based on the virus receptor. We chose a dual-gate field-effect transistor to overcome the low sensitivity of virus-receptor-based biosensors. To optimize the biosensor, we introduced a synthetic virus that mimics the important features of SARS-CoV-2 (size, bilayer structure, and composition). The developed biosensor successfully detected SARS-CoV-2 in 20 min and showed sensitivity comparable to that of molecular diagnostic tests (∼165 copies/mL). Our results indicate that a virus-receptor-based biosensor can be an effective strategy for screening infectious diseases to prevent pandemics.

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Section: Resultsmentioning

confidence: 99%

SARS-CoV-2 Variant Screening Using a Virus-Receptor-Based Electrical Biosensor

et al. 2021

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“…However, we found this catalytic site (Cys144) was next to our solution 2 ( Figure 3 B). To further determine whether hypericin could inhibit the enzymatic activity of 3CLpro, we took advantage of an established FRET assay [ 37 , 38 , 39 ] by using the reporter FRET substrate Dabcyl-YNSTLQ↓AGLRKM-E-Edans. As a start, we expressed the recombinant PEDV 3CLpro with conventional methods of prokaryotic expression, followed by purification with Glutathione Sepharose (GSH) 4B column (GE Healthcare, Chicago, IL, USA) ( Figure 4 A).…”

Section: Resultsmentioning

confidence: 99%

Hypericin Inhibit Alpha-Coronavirus Replication by Targeting 3CL Protease

Zhang

Chen

Zou

et al. 2021

Viruses

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The porcine epidemic diarrhea virus (PEDV) is an Alphacoronavirus (α-CoV) that causes high mortality in infected piglets, resulting in serious economic losses in the farming industry. Hypericin is a dianthrone compound that has been shown as an antiviral activity on several viruses. Here, we first evaluated the antiviral effect of hypericin in PEDV and found the viral replication and egression were significantly reduced with hypericin post-treatment. As hypericin has been shown in SARS-CoV-2 that it is bound to viral 3CLpro, we thus established a molecular docking between hypericin and PEDV 3CLpro using different software and found hypericin bound to 3CLpro through two pockets. These binding pockets were further verified by another docking between hypericin and PEDV 3CLpro pocket mutants, and the fluorescence resonance energy transfer (FRET) assay confirmed that hypericin inhibits the PEDV 3CLpro activity. Moreover, the alignments of α-CoV 3CLpro sequences or crystal structure revealed that the pockets mediating hypericin and PEDV 3CLpro binding were highly conserved, especially in transmissible gastroenteritis virus (TGEV). We then validated the anti-TGEV effect of hypericin through viral replication and egression. Overall, our results push forward that hypericin was for the first time shown to have an inhibitory effect on PEDV and TGEV by targeting 3CLpro, and it deserves further attention as not only a pan-anti-α-CoV compound but potentially also as a compound of other coronaviral infections.

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“…The study opens avenues to develop mutation-free virus detection assays where bioreceptorvirus interaction can be realized as a detection approach. A förster resonance energy transfer (FRET) phenomenon is exploited to develop a SARS-CoV-2-derived RBD ACE2 biosensor [62]. The FRET probe is developed by labelling RBD with YPet and Turquoise2-GL as acceptor and donor, respectively.…”

Section: Ace2-based Optodiagnostics For Covid-19mentioning

confidence: 99%

Angiotensin-converting enzyme 2-based biosensing modalities and devices for coronavirus detection

Gul¹,

Zhai²,

Zhong³

et al. 2022

Preprint

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Rapid and cost-effective diagnostic tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have become a critical and valuable weapon for the coronavirus disease 2019 (COVID-19) pandemic response. SARS-CoV-2 invasion is primarily mediated by human angiotensin-converting enzyme 2 (hACE2). Recent developments in ACE2-based SARS-CoV-2 detection modalities accentuate the potential of this natural host-virus interaction for developing point-of-care (POC) COVID-19 diagnostic tools and devices. Although research on harnessing ACE2 for SARS-CoV-2 detection is in its infancy, some interesting biosensing devices have been developed, showing the commercial viability of this intriguing new approach. The exquisite performance of the reported ACE2-based COVID-19 biosensors provides opportunities for researchers to develop rapid detection tools suitable for testing at points of entry, workplaces, or congregate scenarios in order to effectively implement pandemic control and management plans. However, to be considered as an emerging approach, the rationale for ACE2-based biosensing needs to be critically and comprehensively surveyed and discussed. Herein, we review the current status of ACE2-based detection methods, the signal transduction principles in ACE2 biosensors and the development trend in the future. We discuss the challenges to development of ACE2-biosensors and delineate prospects for their use, along with recommended solutions and suggestions

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Development of a SARS-CoV-2-derived receptor-binding domain-based ACE2 biosensor

Cited by 17 publications

References 39 publications

SARS-CoV-2 Variant Screening Using a Virus-Receptor-Based Electrical Biosensor

SARS-CoV-2 Variant Screening Using a Virus-Receptor-Based Electrical Biosensor

Hypericin Inhibit Alpha-Coronavirus Replication by Targeting 3CL Protease

Angiotensin-converting enzyme 2-based biosensing modalities and devices for coronavirus detection

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