In-Silico Selection of Aptamer Targeting SARS-CoV-2 Spike Protein
Aptamers are single-stranded, short DNA or RNA oligonucleotides that can specifically bind to various target molecules. To diagnose the infected cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in time, numerous conventional methods are applied for viral detection via the amplif...
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| Format: | Article |
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MDPI AG
2022-05-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/10/5810 |
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| author | Yu-Chao Lin Wen-Yih Chen En-Te Hwu Wen-Pin Hu |
| author_facet | Yu-Chao Lin Wen-Yih Chen En-Te Hwu Wen-Pin Hu |
| author_sort | Yu-Chao Lin |
| collection | DOAJ |
| description | Aptamers are single-stranded, short DNA or RNA oligonucleotides that can specifically bind to various target molecules. To diagnose the infected cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in time, numerous conventional methods are applied for viral detection via the amplification and quantification of DNA or antibodies specific to antigens on the virus. Herein, we generated a large number of mutated aptamer sequences, derived from a known sequence of receptor-binding domain (RBD)-1C aptamer, specific to the RBD of SARS-CoV-2 spike protein (S protein). Structural similarity, molecular docking, and molecular dynamics (MD) were utilized to screen aptamers and characterize the detailed interactions between the selected aptamers and the S protein. We identified two mutated aptamers, namely, RBD-1CM1 and RBD-1CM2, which presented better docking results against the S protein compared with the RBD-1C aptamer. Through the MD simulation, we further confirmed that the RBD-1CM1 aptamer can form the most stable complex with the S protein based on the number of hydrogen bonds formed between the two biomolecules. Based on the experimental data of quartz crystal microbalance (QCM), the RBD-1CM1 aptamer could produce larger signals in mass change and exhibit an improved binding affinity to the S protein. Therefore, the RBD-1CM1 aptamer, which was selected from 1431 mutants, was the best potential candidate for the detection of SARS-CoV-2. The RBD-1CM1 aptamer can be an alternative biological element for the development of SARS-CoV-2 diagnostic testing. |
| first_indexed | 2024-03-10T03:42:26Z |
| format | Article |
| id | doaj.art-5d7f2b2e2412492c965702001ab64262 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T03:42:26Z |
| publishDate | 2022-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-5d7f2b2e2412492c965702001ab642622023-11-23T11:28:55ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-05-012310581010.3390/ijms23105810In-Silico Selection of Aptamer Targeting SARS-CoV-2 Spike ProteinYu-Chao Lin0Wen-Yih Chen1En-Te Hwu2Wen-Pin Hu3Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung 404333, TaiwanDepartment of Chemical and Materials Engineering, National Central University, Jhong-Li 32001, TaiwanDepartment of Health Technology, Technical University of Denmark, 2800 Lyngby, DenmarkDepartment of Bioinformatics and Medical Engineering, Asia University, Taichung 41354, TaiwanAptamers are single-stranded, short DNA or RNA oligonucleotides that can specifically bind to various target molecules. To diagnose the infected cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in time, numerous conventional methods are applied for viral detection via the amplification and quantification of DNA or antibodies specific to antigens on the virus. Herein, we generated a large number of mutated aptamer sequences, derived from a known sequence of receptor-binding domain (RBD)-1C aptamer, specific to the RBD of SARS-CoV-2 spike protein (S protein). Structural similarity, molecular docking, and molecular dynamics (MD) were utilized to screen aptamers and characterize the detailed interactions between the selected aptamers and the S protein. We identified two mutated aptamers, namely, RBD-1CM1 and RBD-1CM2, which presented better docking results against the S protein compared with the RBD-1C aptamer. Through the MD simulation, we further confirmed that the RBD-1CM1 aptamer can form the most stable complex with the S protein based on the number of hydrogen bonds formed between the two biomolecules. Based on the experimental data of quartz crystal microbalance (QCM), the RBD-1CM1 aptamer could produce larger signals in mass change and exhibit an improved binding affinity to the S protein. Therefore, the RBD-1CM1 aptamer, which was selected from 1431 mutants, was the best potential candidate for the detection of SARS-CoV-2. The RBD-1CM1 aptamer can be an alternative biological element for the development of SARS-CoV-2 diagnostic testing.https://www.mdpi.com/1422-0067/23/10/5810COVID-19SARS-CoV-2molecular dynamics simulationinfectious diseasespike proteinDNA aptamer |
| spellingShingle | Yu-Chao Lin Wen-Yih Chen En-Te Hwu Wen-Pin Hu In-Silico Selection of Aptamer Targeting SARS-CoV-2 Spike Protein International Journal of Molecular Sciences COVID-19 SARS-CoV-2 molecular dynamics simulation infectious disease spike protein DNA aptamer |
| title | In-Silico Selection of Aptamer Targeting SARS-CoV-2 Spike Protein |
| title_full | In-Silico Selection of Aptamer Targeting SARS-CoV-2 Spike Protein |
| title_fullStr | In-Silico Selection of Aptamer Targeting SARS-CoV-2 Spike Protein |
| title_full_unstemmed | In-Silico Selection of Aptamer Targeting SARS-CoV-2 Spike Protein |
| title_short | In-Silico Selection of Aptamer Targeting SARS-CoV-2 Spike Protein |
| title_sort | in silico selection of aptamer targeting sars cov 2 spike protein |
| topic | COVID-19 SARS-CoV-2 molecular dynamics simulation infectious disease spike protein DNA aptamer |
| url | https://www.mdpi.com/1422-0067/23/10/5810 |
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