Angiotensin-Converting Enzyme 2 (ACE2) As a Novel Biorecognition Element in A Cell-Based Biosensor for the Ultra-Rapid, Ultra-Sensitive Detection of the SARS-CoV-2 S1 Spike Protein Antigen

被引:7
作者
Mavrikou, Sofia [1 ]
Tsekouras, Vasileios [1 ]
Hatziagapiou, Kyriaki [2 ,3 ,4 ]
Tsalidou, Asimina [1 ]
Bakakos, Petros [5 ]
Rovina, Nikoletta [5 ]
Koutsoukou, Antonia [5 ]
Michos, Athanasios [2 ]
Nikola, Olti [2 ]
Koniari, Eleni [6 ,7 ]
Papaparaskevas, Joseph [8 ]
Chrousos, George P. [6 ,7 ]
Kanaka-Gantenbein, Christina [2 ]
Kintzios, Spyridon [1 ]
机构
[1] EU CONEXUS European Univ, Agr Univ Athens, Dept Biotechnol, Lab Cell Technol, Athens 11855, Greece
[2] Natl & Kapodistrian Univ Athens, Agia Sofia Childrens Hosp, Dept Pediat 1, Thivon 1, Athens 11527, Greece
[3] State Univ West Attica, Fac Hlth & Care Sci, Physiotherapy Dept, Agiou Spiridonos 28, Athens 12243, Greece
[4] State Univ West Attica, Fac Hlth & Care Sci, Dept Nursing, Agiou Spiridonos 28, Athens 12243, Greece
[5] Natl & Kapodistrian Univ Athens, Sotiria Hosp, Med Sch, Univ Dept Resp Med 1, 152 Mesogeion Ave, Athens 11527, Greece
[6] Natl & Kapodistrian Univ Athens, Agia Sofia Childrens Hosp, Univ Res Inst Maternal & Child Hlth & Precis Med, Thivon & Livadias 8 Str, Athens 11527, Greece
[7] Natl & Kapodistrian Univ Athens, Agia Sofia Childrens Hosp, UNESCO Chair Adolescent Hlth Care, Thivon & Livadias 8 Str, Athens 11527, Greece
[8] Natl & Kapodistrian Univ Athens, Med Sch, Dept Microbiol, Mikras Asias 75, Athens 11527, Greece
关键词
bioelectric recognition assay (BERA); membrane engineering; public health surveillance; S1 spike protein; rapid antigen test; serological assay; severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2); BIOELECTRIC RECOGNITION ASSAY; RECEPTOR; EXPRESSION; HOMOLOG; BINDING; TARGET; MODEL;
D O I
10.3390/chemosensors9120341
中图分类号
O65 [分析化学];
学科分类号
070302 ; 081704 ;
摘要
Antigen screening for the SARS-CoV-2 S1 spike protein is among the most promising tools for the mass monitoring of asymptomatic carriers of the virus, especially in limited resource environments. Herewith, we report on the possible use of the angiotensin-converting enzyme 2 (ACE2), the natural receptor and entry point of the virus, as a biorecognition element for the detection of the S1 antigen combined with an established bioelectric biosensor based on membrane-engineered cells. The working principle of our approach is based on the measurable change of the electric potential of membrane-engineered mammalian cells bearing ACE2 after attachment of the respective viral protein. We demonstrate that sensitive and selective detection of the S1 antigen is feasible in just three min, with a limit of detection of 20 fg/mL. In a preliminary clinical application, positive patient-derived samples were identified with a 87.9% score compared to RT-PCR. No cross-reactivity was observed against a wide range of nucleocapsid protein concentrations. The novel biosensor is embedded in a commercially ready-to-use testing platform, complete with the consumable immobilized cell-electrode interface and a portable read-out device operable through smartphone or tablet. In addition, the possible application of the system for the high throughput screening of potential pharmacological inhibitors of the ACE2 receptor-S1 RBD interaction is discussed.
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页数:13
相关论文
共 45 条
[1]   Newly Developed System for Acetamiprid Residue Screening in the Lettuce Samples Based on a Bioelectric Cell Biosensor [J].
Apostolou, Theofylaktos ;
Loizou, Konstantinos ;
Hadjilouka, Agni ;
Inglezakis, Antonios ;
Kintzios, Spyridon .
BIOSENSORS-BASEL, 2020, 10 (02)
[2]  
ARMBRUSTER DA, 1994, CLIN CHEM, V40, P1233
[3]   Amino acids 270 to 510 of the severe acute respiratory syndrome coronavirus spike protein are required for interaction with receptor [J].
Babcock, GJ ;
Esshaki, DJ ;
Thomas, WD ;
Ambrosino, DM .
JOURNAL OF VIROLOGY, 2004, 78 (09) :4552-4560
[4]   Sensitivity of SARS-CoV-2 Detection With Nasopharyngeal Swabs [J].
Clerici, Bianca ;
Muscatello, Antonio ;
Bai, Francesca ;
Pavanello, Donatella ;
Orlandi, Michela ;
Marchetti, Giulia C. ;
Castelli, Valeria ;
Casazza, Giovanni ;
Costantino, Giorgio ;
Podda, Gian Marco .
FRONTIERS IN PUBLIC HEALTH, 2021, 8
[5]   Why Does the Novel Coronavirus Spike Protein Interact so Strongly with the Human ACE2? A Thermodynamic Answer [J].
de Andrade, Jones ;
Goncalves, Paulo Fernando Bruno ;
Netz, Paulo Augusto .
CHEMBIOCHEM, 2021, 22 (05) :865-875
[6]   Minute-scale detection of SARS-CoV-2 using a low-cost biosensor composed of pencil graphite electrodes [J].
de Lima, Lucas F. ;
Ferreira, Andre L. ;
Torres, Marcelo D. T. ;
de Araujo, William R. ;
de la Fuente-Nunez, Cesar .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2021, 118 (30)
[7]   New Insights Into the Physiopathology of COVID-19: SARS-CoV-2-Associated Gastrointestinal Illness [J].
Devaux, Christian A. ;
Lagier, Jean-Christophe ;
Raoult, Didier .
FRONTIERS IN MEDICINE, 2021, 8
[8]   Computational Design of ACE2-Based Peptide Inhibitors of SARS-CoV-2 [J].
Han, Yanxiao ;
Kral, Petr .
ACS NANO, 2020, 14 (04) :5143-5147
[9]   Quantitative mRNA expression profiling of ACE 2, a novel homologue of angiotensin converting enzyme [J].
Harmer, D ;
Gilbert, M ;
Borman, R ;
Clark, KL .
FEBS LETTERS, 2002, 532 (1-2) :107-110
[10]  
Joyce M Gordon, 2020, bioRxiv, DOI 10.1101/2020.03.15.992883