Development of flexible electrochemical impedance spectroscopy-based biosensing platform for rapid screening of SARS-CoV-2 inhibitors
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters the cells through the binding of its spike protein (S-protein) to the cell surface-expressing angiotensin-converting enzyme 2 (ACE2). Thus, inhibition of S-protein-ACE2 binding may impede SARS-CoV-2 cell entry and attenuate the prog...
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| creator | Kiew, Lik-Voon Chang, Chia-Yu Huang, Sheng-Yu Wang, Pei-Wen Heh, Choon-Han Liu, Chung-Te Cheng, Chia-Hsin Lu, Yi-Xiang Chen, Yen-Chen Huang, Yi-Xuan Chang, Sheng-Yun Tsai, Huei-Yu Kung, Yu-An Huang, Peng-Nien Hsu, Ming-Hua Leo, Bey-Fen Foo, Yiing-Yee Su, Chien-Hao Hsu, Kuo-Chen Huang, Po-Hsun Ng, Chirk-Jenn Kamarulzaman, Adeeba Yuan, Chiun-Jye Shieh, Dar-Bin Shih, Shin-Ru Chung, Lip-Yong Chang, Chia-Ching |
| description | Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters the cells through the binding of its spike protein (S-protein) to the cell surface-expressing angiotensin-converting enzyme 2 (ACE2). Thus, inhibition of S-protein-ACE2 binding may impede SARS-CoV-2 cell entry and attenuate the progression of Coronavirus disease 2019 (COVID-19). In this study, an electrochemical impedance spectroscopy-based biosensing platform consisting of a recombinant ACE2-coated palladium nano-thin-film electrode as the core sensing element was fabricated for the screening of potential inhibitors against S-protein-ACE2 binding. The platform could detect interference of small analytes against S-protein-ACE2 binding at low analyte concentration and small volume (0.1 μg/mL and ~1 μL, estimated total analyte consumption |
| doi_str_mv | 10.1016/j.bios.2021.113213 |
| format | Article |
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•A sensitive sensing platform was developed to detect modulators that affect the SARS-CoV-2 and ACE2 interaction.•The modulators can be detected in a small volume of 1 μL with the total analyte consumption <4 pg.•The bio-probes can be conjugated to the flexible nano-Pd thin film electrode can be achieved within 15–20 min.•Potential leads, i.e., ramiprilat, and perindoprilat, that reduce the risks of the SARS-CoV-2 infection were identified.</description><identifier>ISSN: 0956-5663</identifier><identifier>EISSN: 1873-4235</identifier><identifier>DOI: 10.1016/j.bios.2021.113213</identifier><identifier>PMID: 33857754</identifier><language>eng</language><publisher>England: Elsevier B.V</publisher><subject>ACE2-SARS CoV 2 S-Protein interaction ; Biosensing Techniques ; Biosensor ; COVID-19 ; Dielectric Spectroscopy ; Electrochemical impedance spectroscopy (EIS) ; Humans ; Palladium nano-thin-film electrode ; Protein Binding ; SARS-CoV-2 ; SARS-CoV-2 infection inhibitors ; Spike Glycoprotein, Coronavirus</subject><ispartof>Biosensors & bioelectronics, 2021-07, Vol.183, p.113213-113213, Article 113213</ispartof><rights>2021 The Author(s)</rights><rights>Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.</rights><rights>2021 The Author(s) 2021</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c455t-cdd6d93506ddf2ec6be143675d817c5fc6c562452ea76b352f257ef11e842a213</citedby><cites>FETCH-LOGICAL-c455t-cdd6d93506ddf2ec6be143675d817c5fc6c562452ea76b352f257ef11e842a213</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0956566321002505$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>230,314,776,780,881,3537,27901,27902,65534</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33857754$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kiew, Lik-Voon</creatorcontrib><creatorcontrib>Chang, Chia-Yu</creatorcontrib><creatorcontrib>Huang, Sheng-Yu</creatorcontrib><creatorcontrib>Wang, Pei-Wen</creatorcontrib><creatorcontrib>Heh, Choon-Han</creatorcontrib><creatorcontrib>Liu, Chung-Te</creatorcontrib><creatorcontrib>Cheng, Chia-Hsin</creatorcontrib><creatorcontrib>Lu, Yi-Xiang</creatorcontrib><creatorcontrib>Chen, Yen-Chen</creatorcontrib><creatorcontrib>Huang, Yi-Xuan</creatorcontrib><creatorcontrib>Chang, Sheng-Yun</creatorcontrib><creatorcontrib>Tsai, Huei-Yu</creatorcontrib><creatorcontrib>Kung, Yu-An</creatorcontrib><creatorcontrib>Huang, Peng-Nien</creatorcontrib><creatorcontrib>Hsu, Ming-Hua</creatorcontrib><creatorcontrib>Leo, Bey-Fen</creatorcontrib><creatorcontrib>Foo, Yiing-Yee</creatorcontrib><creatorcontrib>Su, Chien-Hao</creatorcontrib><creatorcontrib>Hsu, Kuo-Chen</creatorcontrib><creatorcontrib>Huang, Po-Hsun</creatorcontrib><creatorcontrib>Ng, Chirk-Jenn</creatorcontrib><creatorcontrib>Kamarulzaman, Adeeba</creatorcontrib><creatorcontrib>Yuan, Chiun-Jye</creatorcontrib><creatorcontrib>Shieh, Dar-Bin</creatorcontrib><creatorcontrib>Shih, Shin-Ru</creatorcontrib><creatorcontrib>Chung, Lip-Yong</creatorcontrib><creatorcontrib>Chang, Chia-Ching</creatorcontrib><title>Development of flexible electrochemical impedance spectroscopy-based biosensing platform for rapid screening of SARS-CoV-2 inhibitors</title><title>Biosensors & bioelectronics</title><addtitle>Biosens Bioelectron</addtitle><description>Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters the cells through the binding of its spike protein (S-protein) to the cell surface-expressing angiotensin-converting enzyme 2 (ACE2). Thus, inhibition of S-protein-ACE2 binding may impede SARS-CoV-2 cell entry and attenuate the progression of Coronavirus disease 2019 (COVID-19). In this study, an electrochemical impedance spectroscopy-based biosensing platform consisting of a recombinant ACE2-coated palladium nano-thin-film electrode as the core sensing element was fabricated for the screening of potential inhibitors against S-protein-ACE2 binding. The platform could detect interference of small analytes against S-protein-ACE2 binding at low analyte concentration and small volume (0.1 μg/mL and ~1 μL, estimated total analyte consumption < 4 pg) within 21 min. Thus, a few potential inhibitors of S-protein-ACE2 binding were identified. This includes (2S,3aS,6aS)-1-((S)–N-((S)-1-Carboxy-3-phenylpropyl)alanyl)tetrahydrocyclopenta[b] pyrrole-2-carboxylic acid (ramiprilat) and (2S,3aS,7aS)-1-[(2S)-2-[[(2S)-1-Carboxybutyl]amino]propanoyl]-2,3,3a,4,5,6,7,7a-octahydroindole-2-carboxylic acid (perindoprilat) that reduced the binding affinity of S-protein to ACE2 by 72% and 67%; and SARS-CoV-2 in vitro infectivity to the ACE2-expressing human oral cavity squamous carcinoma cells (OEC-M1) by 36.4 and 20.1%, respectively, compared to the PBS control. These findings demonstrated the usefulness of the developed biosensing platform for the rapid screening of modulators for S-protein-ACE2 binding.
•A sensitive sensing platform was developed to detect modulators that affect the SARS-CoV-2 and ACE2 interaction.•The modulators can be detected in a small volume of 1 μL with the total analyte consumption <4 pg.•The bio-probes can be conjugated to the flexible nano-Pd thin film electrode can be achieved within 15–20 min.•Potential leads, i.e., ramiprilat, and perindoprilat, that reduce the risks of the SARS-CoV-2 infection were identified.</description><subject>ACE2-SARS CoV 2 S-Protein interaction</subject><subject>Biosensing Techniques</subject><subject>Biosensor</subject><subject>COVID-19</subject><subject>Dielectric Spectroscopy</subject><subject>Electrochemical impedance spectroscopy (EIS)</subject><subject>Humans</subject><subject>Palladium nano-thin-film electrode</subject><subject>Protein Binding</subject><subject>SARS-CoV-2</subject><subject>SARS-CoV-2 infection inhibitors</subject><subject>Spike Glycoprotein, Coronavirus</subject><issn>0956-5663</issn><issn>1873-4235</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9UU1v1DAUtBAVXQp_gAPykUsWf8ROIiGkaksBqVIlClwtx37ueuXEwc6u6A_gf9dhSwUXLvZh5s28N4PQK0rWlFD5drfufcxrRhhdU8oZ5U_QirYNr2rGxVO0Ip2QlZCSn6LnOe8IIQ3tyDN0ynkrmkbUK_TrAg4Q4jTAOOPosAvw0_cBMAQwc4pmC4M3OmA_TGD1aADn6TeSTZzuql5nsHjZA8bsx1s8BT27mAZcHpz05C3OJgGMC1gMbs6_3FSb-L1i2I9b3_s5pvwCnTgdMrx8-M_Qt8sPXzefqqvrj58351eVqYWYK2OttB0XRFrrGBjZA625bIRtaWOEM9IIyWrBQDey54I5JhpwlEJbM13yOUPvj7rTvh_AmnJ00kFNyQ863amovfoXGf1W3caDagltOyKKwJsHgRR_7CHPavDZQAh6hLjPiglai47TdvFiR6opWeUE7tGGErX0p3ZqyU0t_aljf2Xo9d8LPo78KawQ3h0JUGI6eEgqGw-lFutTqUXZ6P-nfw-5ea_k</recordid><startdate>20210701</startdate><enddate>20210701</enddate><creator>Kiew, Lik-Voon</creator><creator>Chang, Chia-Yu</creator><creator>Huang, Sheng-Yu</creator><creator>Wang, Pei-Wen</creator><creator>Heh, Choon-Han</creator><creator>Liu, Chung-Te</creator><creator>Cheng, Chia-Hsin</creator><creator>Lu, Yi-Xiang</creator><creator>Chen, Yen-Chen</creator><creator>Huang, Yi-Xuan</creator><creator>Chang, Sheng-Yun</creator><creator>Tsai, Huei-Yu</creator><creator>Kung, Yu-An</creator><creator>Huang, Peng-Nien</creator><creator>Hsu, Ming-Hua</creator><creator>Leo, Bey-Fen</creator><creator>Foo, Yiing-Yee</creator><creator>Su, Chien-Hao</creator><creator>Hsu, Kuo-Chen</creator><creator>Huang, Po-Hsun</creator><creator>Ng, Chirk-Jenn</creator><creator>Kamarulzaman, Adeeba</creator><creator>Yuan, Chiun-Jye</creator><creator>Shieh, Dar-Bin</creator><creator>Shih, Shin-Ru</creator><creator>Chung, Lip-Yong</creator><creator>Chang, Chia-Ching</creator><general>Elsevier B.V</general><general>The Author(s). Published by Elsevier B.V</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20210701</creationdate><title>Development of flexible electrochemical impedance spectroscopy-based biosensing platform for rapid screening of SARS-CoV-2 inhibitors</title><author>Kiew, Lik-Voon ; Chang, Chia-Yu ; Huang, Sheng-Yu ; Wang, Pei-Wen ; Heh, Choon-Han ; Liu, Chung-Te ; Cheng, Chia-Hsin ; Lu, Yi-Xiang ; Chen, Yen-Chen ; Huang, Yi-Xuan ; Chang, Sheng-Yun ; Tsai, Huei-Yu ; Kung, Yu-An ; Huang, Peng-Nien ; Hsu, Ming-Hua ; Leo, Bey-Fen ; Foo, Yiing-Yee ; Su, Chien-Hao ; Hsu, Kuo-Chen ; Huang, Po-Hsun ; Ng, Chirk-Jenn ; Kamarulzaman, Adeeba ; Yuan, Chiun-Jye ; Shieh, Dar-Bin ; Shih, Shin-Ru ; Chung, Lip-Yong ; Chang, Chia-Ching</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c455t-cdd6d93506ddf2ec6be143675d817c5fc6c562452ea76b352f257ef11e842a213</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>ACE2-SARS CoV 2 S-Protein interaction</topic><topic>Biosensing Techniques</topic><topic>Biosensor</topic><topic>COVID-19</topic><topic>Dielectric Spectroscopy</topic><topic>Electrochemical impedance spectroscopy (EIS)</topic><topic>Humans</topic><topic>Palladium nano-thin-film electrode</topic><topic>Protein Binding</topic><topic>SARS-CoV-2</topic><topic>SARS-CoV-2 infection inhibitors</topic><topic>Spike Glycoprotein, Coronavirus</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kiew, Lik-Voon</creatorcontrib><creatorcontrib>Chang, Chia-Yu</creatorcontrib><creatorcontrib>Huang, Sheng-Yu</creatorcontrib><creatorcontrib>Wang, Pei-Wen</creatorcontrib><creatorcontrib>Heh, Choon-Han</creatorcontrib><creatorcontrib>Liu, Chung-Te</creatorcontrib><creatorcontrib>Cheng, Chia-Hsin</creatorcontrib><creatorcontrib>Lu, Yi-Xiang</creatorcontrib><creatorcontrib>Chen, Yen-Chen</creatorcontrib><creatorcontrib>Huang, Yi-Xuan</creatorcontrib><creatorcontrib>Chang, Sheng-Yun</creatorcontrib><creatorcontrib>Tsai, Huei-Yu</creatorcontrib><creatorcontrib>Kung, Yu-An</creatorcontrib><creatorcontrib>Huang, Peng-Nien</creatorcontrib><creatorcontrib>Hsu, Ming-Hua</creatorcontrib><creatorcontrib>Leo, Bey-Fen</creatorcontrib><creatorcontrib>Foo, Yiing-Yee</creatorcontrib><creatorcontrib>Su, Chien-Hao</creatorcontrib><creatorcontrib>Hsu, Kuo-Chen</creatorcontrib><creatorcontrib>Huang, Po-Hsun</creatorcontrib><creatorcontrib>Ng, Chirk-Jenn</creatorcontrib><creatorcontrib>Kamarulzaman, Adeeba</creatorcontrib><creatorcontrib>Yuan, Chiun-Jye</creatorcontrib><creatorcontrib>Shieh, Dar-Bin</creatorcontrib><creatorcontrib>Shih, Shin-Ru</creatorcontrib><creatorcontrib>Chung, Lip-Yong</creatorcontrib><creatorcontrib>Chang, Chia-Ching</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Biosensors & bioelectronics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kiew, Lik-Voon</au><au>Chang, Chia-Yu</au><au>Huang, Sheng-Yu</au><au>Wang, Pei-Wen</au><au>Heh, Choon-Han</au><au>Liu, Chung-Te</au><au>Cheng, Chia-Hsin</au><au>Lu, Yi-Xiang</au><au>Chen, Yen-Chen</au><au>Huang, Yi-Xuan</au><au>Chang, Sheng-Yun</au><au>Tsai, Huei-Yu</au><au>Kung, Yu-An</au><au>Huang, Peng-Nien</au><au>Hsu, Ming-Hua</au><au>Leo, Bey-Fen</au><au>Foo, Yiing-Yee</au><au>Su, Chien-Hao</au><au>Hsu, Kuo-Chen</au><au>Huang, Po-Hsun</au><au>Ng, Chirk-Jenn</au><au>Kamarulzaman, Adeeba</au><au>Yuan, Chiun-Jye</au><au>Shieh, Dar-Bin</au><au>Shih, Shin-Ru</au><au>Chung, Lip-Yong</au><au>Chang, Chia-Ching</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Development of flexible electrochemical impedance spectroscopy-based biosensing platform for rapid screening of SARS-CoV-2 inhibitors</atitle><jtitle>Biosensors & bioelectronics</jtitle><addtitle>Biosens Bioelectron</addtitle><date>2021-07-01</date><risdate>2021</risdate><volume>183</volume><spage>113213</spage><epage>113213</epage><pages>113213-113213</pages><artnum>113213</artnum><issn>0956-5663</issn><eissn>1873-4235</eissn><abstract>Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters the cells through the binding of its spike protein (S-protein) to the cell surface-expressing angiotensin-converting enzyme 2 (ACE2). Thus, inhibition of S-protein-ACE2 binding may impede SARS-CoV-2 cell entry and attenuate the progression of Coronavirus disease 2019 (COVID-19). In this study, an electrochemical impedance spectroscopy-based biosensing platform consisting of a recombinant ACE2-coated palladium nano-thin-film electrode as the core sensing element was fabricated for the screening of potential inhibitors against S-protein-ACE2 binding. The platform could detect interference of small analytes against S-protein-ACE2 binding at low analyte concentration and small volume (0.1 μg/mL and ~1 μL, estimated total analyte consumption < 4 pg) within 21 min. Thus, a few potential inhibitors of S-protein-ACE2 binding were identified. This includes (2S,3aS,6aS)-1-((S)–N-((S)-1-Carboxy-3-phenylpropyl)alanyl)tetrahydrocyclopenta[b] pyrrole-2-carboxylic acid (ramiprilat) and (2S,3aS,7aS)-1-[(2S)-2-[[(2S)-1-Carboxybutyl]amino]propanoyl]-2,3,3a,4,5,6,7,7a-octahydroindole-2-carboxylic acid (perindoprilat) that reduced the binding affinity of S-protein to ACE2 by 72% and 67%; and SARS-CoV-2 in vitro infectivity to the ACE2-expressing human oral cavity squamous carcinoma cells (OEC-M1) by 36.4 and 20.1%, respectively, compared to the PBS control. These findings demonstrated the usefulness of the developed biosensing platform for the rapid screening of modulators for S-protein-ACE2 binding.
•A sensitive sensing platform was developed to detect modulators that affect the SARS-CoV-2 and ACE2 interaction.•The modulators can be detected in a small volume of 1 μL with the total analyte consumption <4 pg.•The bio-probes can be conjugated to the flexible nano-Pd thin film electrode can be achieved within 15–20 min.•Potential leads, i.e., ramiprilat, and perindoprilat, that reduce the risks of the SARS-CoV-2 infection were identified.</abstract><cop>England</cop><pub>Elsevier B.V</pub><pmid>33857754</pmid><doi>10.1016/j.bios.2021.113213</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Biosensors & bioelectronics, 2021-07, Vol.183, p.113213-113213, Article 113213 |
| issn | 0956-5663 1873-4235 |
| language | eng |
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| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | ACE2-SARS CoV 2 S-Protein interaction Biosensing Techniques Biosensor COVID-19 Dielectric Spectroscopy Electrochemical impedance spectroscopy (EIS) Humans Palladium nano-thin-film electrode Protein Binding SARS-CoV-2 SARS-CoV-2 infection inhibitors Spike Glycoprotein, Coronavirus |
| title | Development of flexible electrochemical impedance spectroscopy-based biosensing platform for rapid screening of SARS-CoV-2 inhibitors |
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