Kinetics of Drug Molecule Interactions with a Newly Developed Nano-Gold-Modified Spike Protein Electrochemical Receptor Sensor
In March 2020, the World Health Organization (WHO) declared COVID-19 a pandemic, and the spike protein has been reported to be an important drug target for anti-COVID-19 treatment. As such, in this study, we successfully developed a novel electrochemical receptor biosensor by immobilizing the SARS-C...
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| Format: | Article |
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MDPI AG
2022-10-01
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| Series: | Biosensors |
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| Online Access: | https://www.mdpi.com/2079-6374/12/10/888 |
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| author | Dingqiang Lu Danyang Liu Xinqian Wang Yujiao Liu Yixuan Liu Ruijuan Ren Guangchang Pang |
| author_facet | Dingqiang Lu Danyang Liu Xinqian Wang Yujiao Liu Yixuan Liu Ruijuan Ren Guangchang Pang |
| author_sort | Dingqiang Lu |
| collection | DOAJ |
| description | In March 2020, the World Health Organization (WHO) declared COVID-19 a pandemic, and the spike protein has been reported to be an important drug target for anti-COVID-19 treatment. As such, in this study, we successfully developed a novel electrochemical receptor biosensor by immobilizing the SARS-CoV-2 spike protein and using AuNPs-HRP as an electrochemical signal amplification system. Moreover, the time-current method was used to quantify seven antiviral drug compounds, such as arbidol and chloroquine diphosphate. The results show that the spike protein and the drugs are linearly correlated within a certain concentration range and that the detection sensitivity of the sensor is extremely high. In the low concentration range of linear response, the kinetics of receptor–ligand interactions are similar to that of an enzymatic reaction. Among the investigated drug molecules, bromhexine exhibits the smallest Ka value, and thus, is most sensitively detected by the sensor. Hydroxychloroquine exhibits the largest Ka value. Molecular docking simulations of the spike protein with six small-molecule drugs show that residues of this protein, such as Asp, Trp, Asn, and Gln, form hydrogen bonds with the -OH or -NH<sub>2</sub> groups on the branched chains of small-molecule drugs. The electrochemical receptor biosensor can directly quantify the interaction between the spike protein and drugs such as abidor and hydroxychloroquine and perform kinetic studies with a limit of detection 3.3 × 10<sup>−</sup><sup>20</sup> mol/L, which provides a new research method and idea for receptor–ligand interactions and pharmacodynamic evaluation. |
| first_indexed | 2024-03-09T20:36:03Z |
| format | Article |
| id | doaj.art-7d3d7b6747a045ec915255ef5c136497 |
| institution | Directory Open Access Journal |
| issn | 2079-6374 |
| language | English |
| last_indexed | 2024-03-09T20:36:03Z |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biosensors |
| spelling | doaj.art-7d3d7b6747a045ec915255ef5c1364972023-11-23T23:12:16ZengMDPI AGBiosensors2079-63742022-10-01121088810.3390/bios12100888Kinetics of Drug Molecule Interactions with a Newly Developed Nano-Gold-Modified Spike Protein Electrochemical Receptor SensorDingqiang Lu0Danyang Liu1Xinqian Wang2Yujiao Liu3Yixuan Liu4Ruijuan Ren5Guangchang Pang6College of Biotechnology & Food Science, Tianjin University of Commerce, Tianjin 300134, ChinaCollege of Biotechnology & Food Science, Tianjin University of Commerce, Tianjin 300134, ChinaCollege of Biotechnology & Food Science, Tianjin University of Commerce, Tianjin 300134, ChinaCollege of Biotechnology & Food Science, Tianjin University of Commerce, Tianjin 300134, ChinaCollege of Biotechnology & Food Science, Tianjin University of Commerce, Tianjin 300134, ChinaTianjin Institute for Food Safety Inspection Technology, Tianjin 300134, ChinaCollege of Biotechnology & Food Science, Tianjin University of Commerce, Tianjin 300134, ChinaIn March 2020, the World Health Organization (WHO) declared COVID-19 a pandemic, and the spike protein has been reported to be an important drug target for anti-COVID-19 treatment. As such, in this study, we successfully developed a novel electrochemical receptor biosensor by immobilizing the SARS-CoV-2 spike protein and using AuNPs-HRP as an electrochemical signal amplification system. Moreover, the time-current method was used to quantify seven antiviral drug compounds, such as arbidol and chloroquine diphosphate. The results show that the spike protein and the drugs are linearly correlated within a certain concentration range and that the detection sensitivity of the sensor is extremely high. In the low concentration range of linear response, the kinetics of receptor–ligand interactions are similar to that of an enzymatic reaction. Among the investigated drug molecules, bromhexine exhibits the smallest Ka value, and thus, is most sensitively detected by the sensor. Hydroxychloroquine exhibits the largest Ka value. Molecular docking simulations of the spike protein with six small-molecule drugs show that residues of this protein, such as Asp, Trp, Asn, and Gln, form hydrogen bonds with the -OH or -NH<sub>2</sub> groups on the branched chains of small-molecule drugs. The electrochemical receptor biosensor can directly quantify the interaction between the spike protein and drugs such as abidor and hydroxychloroquine and perform kinetic studies with a limit of detection 3.3 × 10<sup>−</sup><sup>20</sup> mol/L, which provides a new research method and idea for receptor–ligand interactions and pharmacodynamic evaluation.https://www.mdpi.com/2079-6374/12/10/888SARS-CoV-2spike proteinelectrochemical receptor biosensorlinkage allosterism |
| spellingShingle | Dingqiang Lu Danyang Liu Xinqian Wang Yujiao Liu Yixuan Liu Ruijuan Ren Guangchang Pang Kinetics of Drug Molecule Interactions with a Newly Developed Nano-Gold-Modified Spike Protein Electrochemical Receptor Sensor Biosensors SARS-CoV-2 spike protein electrochemical receptor biosensor linkage allosterism |
| title | Kinetics of Drug Molecule Interactions with a Newly Developed Nano-Gold-Modified Spike Protein Electrochemical Receptor Sensor |
| title_full | Kinetics of Drug Molecule Interactions with a Newly Developed Nano-Gold-Modified Spike Protein Electrochemical Receptor Sensor |
| title_fullStr | Kinetics of Drug Molecule Interactions with a Newly Developed Nano-Gold-Modified Spike Protein Electrochemical Receptor Sensor |
| title_full_unstemmed | Kinetics of Drug Molecule Interactions with a Newly Developed Nano-Gold-Modified Spike Protein Electrochemical Receptor Sensor |
| title_short | Kinetics of Drug Molecule Interactions with a Newly Developed Nano-Gold-Modified Spike Protein Electrochemical Receptor Sensor |
| title_sort | kinetics of drug molecule interactions with a newly developed nano gold modified spike protein electrochemical receptor sensor |
| topic | SARS-CoV-2 spike protein electrochemical receptor biosensor linkage allosterism |
| url | https://www.mdpi.com/2079-6374/12/10/888 |
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