Effect of the N501Y Mutation on Ligands Complexed with SARS-CoV-2 RBD: Insights on Potential Drug Candidates for COVID-19
Bioactive compounds against SARS-CoV-2 targets could be potential treatments for COVID-19. Inhibitors of the receptor-binding domain (RBD) on the viral spike protein can block its binding to the human angiotensin-converting enzyme type II (ACE2) receptor. This study presents ligands based on natural...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-05-01
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| Series: | Drugs and Drug Candidates |
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| Online Access: | https://www.mdpi.com/2813-2998/2/2/22 |
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| author | Camila Fonseca Amorim da Silva Samanta Omae Camalhonte Michell de Oliveira Almeida Sheila Cruz Araujo Miriam Sannomiya João Henrique Ghilardi Lago Kathia Maria Honorio |
| author_facet | Camila Fonseca Amorim da Silva Samanta Omae Camalhonte Michell de Oliveira Almeida Sheila Cruz Araujo Miriam Sannomiya João Henrique Ghilardi Lago Kathia Maria Honorio |
| author_sort | Camila Fonseca Amorim da Silva |
| collection | DOAJ |
| description | Bioactive compounds against SARS-CoV-2 targets could be potential treatments for COVID-19. Inhibitors of the receptor-binding domain (RBD) on the viral spike protein can block its binding to the human angiotensin-converting enzyme type II (ACE2) receptor. This study presents ligands based on natural products and synthetic compounds, targeting multiple N501/Y501 RBDs, besides RBD-ACE2, over different regions. The selected compounds were evaluated by docking using consensus scoring, pharmacokinetics/toxicological analyses, and molecular dynamics. Additionally, N501/Y501 RBD-ACE2 interaction properties and RBD–ligand complexes were compared. We identified that coenzyme Q10, 1-stearoyl-2-arachidonoylglycerol, and palmitone showed the greatest RBD interactions. Targeting specific residues (in particular, tyrosine) in the C-, N-terminal, and central RBD sites promoted more stable protein–ligand interactions than in the N-terminal region only. Our results indicate that the molecules had more energetically favorable interactions with residues from distinct RBD regions rather than only interacting with residues in the N-terminal site. Moreover, the compounds might better interact with mutated N501Y than N501 RBDs. These hits can be optimized to leads and investigated through QSAR models and biological assays to comprehend mechanisms better. Altogether, such strategies may anticipate antiviral strategies if or when future variants and other CoVs arise. |
| first_indexed | 2024-03-11T00:29:00Z |
| format | Article |
| id | doaj.art-05edf5cd355e4bd29bd4ec1fb3aa906f |
| institution | Directory Open Access Journal |
| issn | 2813-2998 |
| language | English |
| last_indexed | 2024-03-11T00:29:00Z |
| publishDate | 2023-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Drugs and Drug Candidates |
| spelling | doaj.art-05edf5cd355e4bd29bd4ec1fb3aa906f2023-11-18T22:45:50ZengMDPI AGDrugs and Drug Candidates2813-29982023-05-012243345810.3390/ddc2020022Effect of the N501Y Mutation on Ligands Complexed with SARS-CoV-2 RBD: Insights on Potential Drug Candidates for COVID-19Camila Fonseca Amorim da Silva0Samanta Omae Camalhonte1Michell de Oliveira Almeida2Sheila Cruz Araujo3Miriam Sannomiya4João Henrique Ghilardi Lago5Kathia Maria Honorio6School of Arts, Sciences and Humanities, University of Sao Paulo, Sao Paulo 03828-000, BrazilSchool of Arts, Sciences and Humanities, University of Sao Paulo, Sao Paulo 03828-000, BrazilDepartment of Chemistry and Molecular Physics, Chemistry Institute of Sao Carlos, University of Sao Paulo, Sao Carlos 13566-590, BrazilNatural and Human Sciences Center, Federal University of A.B.C., Santo Andre 09210-580, BrazilSchool of Arts, Sciences and Humanities, University of Sao Paulo, Sao Paulo 03828-000, BrazilNatural and Human Sciences Center, Federal University of A.B.C., Santo Andre 09210-580, BrazilSchool of Arts, Sciences and Humanities, University of Sao Paulo, Sao Paulo 03828-000, BrazilBioactive compounds against SARS-CoV-2 targets could be potential treatments for COVID-19. Inhibitors of the receptor-binding domain (RBD) on the viral spike protein can block its binding to the human angiotensin-converting enzyme type II (ACE2) receptor. This study presents ligands based on natural products and synthetic compounds, targeting multiple N501/Y501 RBDs, besides RBD-ACE2, over different regions. The selected compounds were evaluated by docking using consensus scoring, pharmacokinetics/toxicological analyses, and molecular dynamics. Additionally, N501/Y501 RBD-ACE2 interaction properties and RBD–ligand complexes were compared. We identified that coenzyme Q10, 1-stearoyl-2-arachidonoylglycerol, and palmitone showed the greatest RBD interactions. Targeting specific residues (in particular, tyrosine) in the C-, N-terminal, and central RBD sites promoted more stable protein–ligand interactions than in the N-terminal region only. Our results indicate that the molecules had more energetically favorable interactions with residues from distinct RBD regions rather than only interacting with residues in the N-terminal site. Moreover, the compounds might better interact with mutated N501Y than N501 RBDs. These hits can be optimized to leads and investigated through QSAR models and biological assays to comprehend mechanisms better. Altogether, such strategies may anticipate antiviral strategies if or when future variants and other CoVs arise.https://www.mdpi.com/2813-2998/2/2/22COVID-19SARS-CoV-2spikedrug discoveryin silico strategiesdocking |
| spellingShingle | Camila Fonseca Amorim da Silva Samanta Omae Camalhonte Michell de Oliveira Almeida Sheila Cruz Araujo Miriam Sannomiya João Henrique Ghilardi Lago Kathia Maria Honorio Effect of the N501Y Mutation on Ligands Complexed with SARS-CoV-2 RBD: Insights on Potential Drug Candidates for COVID-19 Drugs and Drug Candidates COVID-19 SARS-CoV-2 spike drug discovery in silico strategies docking |
| title | Effect of the N501Y Mutation on Ligands Complexed with SARS-CoV-2 RBD: Insights on Potential Drug Candidates for COVID-19 |
| title_full | Effect of the N501Y Mutation on Ligands Complexed with SARS-CoV-2 RBD: Insights on Potential Drug Candidates for COVID-19 |
| title_fullStr | Effect of the N501Y Mutation on Ligands Complexed with SARS-CoV-2 RBD: Insights on Potential Drug Candidates for COVID-19 |
| title_full_unstemmed | Effect of the N501Y Mutation on Ligands Complexed with SARS-CoV-2 RBD: Insights on Potential Drug Candidates for COVID-19 |
| title_short | Effect of the N501Y Mutation on Ligands Complexed with SARS-CoV-2 RBD: Insights on Potential Drug Candidates for COVID-19 |
| title_sort | effect of the n501y mutation on ligands complexed with sars cov 2 rbd insights on potential drug candidates for covid 19 |
| topic | COVID-19 SARS-CoV-2 spike drug discovery in silico strategies docking |
| url | https://www.mdpi.com/2813-2998/2/2/22 |
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