Glycosylation as a key for enhancing drug recognition into spike glycoprotein of SARS-CoV-2
The emergence of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and its spread since 2019 represents the major public health problem worldwide nowadays, generating a high number of infections and deaths. That’s why, in addition to vaccination campaigns, the design of a drug to help...
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2021
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| author | Georcki Ropón‐Palacios Jhon Pérez-Silva Ricardo Rojas-Humpire Gustavo E. Olivos-Ramírez Manuel Enrique Chenet Zuta Víctor Villanueva Sheyla Carmen-Sifuentes Kewin Otazu Yaritza L. Ramirez-Díaz Ihosvany Camps |
| author_browse | Georcki Ropón‐Palacios Gustavo E. Olivos-Ramírez Ihosvany Camps Jhon Pérez-Silva Kewin Otazu Manuel Enrique Chenet Zuta Ricardo Rojas-Humpire Sheyla Carmen-Sifuentes Víctor Villanueva Yaritza L. Ramirez-Díaz |
| author_facet | Georcki Ropón‐Palacios Jhon Pérez-Silva Ricardo Rojas-Humpire Gustavo E. Olivos-Ramírez Manuel Enrique Chenet Zuta Víctor Villanueva Sheyla Carmen-Sifuentes Kewin Otazu Yaritza L. Ramirez-Díaz Ihosvany Camps |
| author_sort | Georcki Ropón‐Palacios |
| collection | Producción científica |
| description | The emergence of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and its spread since 2019 represents the major public health problem worldwide nowadays, generating a high number of infections and deaths. That’s why, in addition to vaccination campaigns, the design of a drug to help in the treatment of severe cases of COVID-19 is being investigated. In relation to SARS-CoV-2, one of its most studied proteins is the spike protein (S protein), which mediates host-cell entry and is heavily glycosylated. Regarding the latter, several investigations have been carried out, since it plays an important role in the evasion of the host's immune system and contributes to protein folding and the thermostability of the viral particle. For that reason, our objective was to evaluate the impact of glycosylations on the drug recognition on two domains of the S protein, the receptor-binding domain (RBD) and the N-terminal domain (NTD) through molecular dynamics simulations and computational biophysics analysis. Our results show that glycosylations in the S protein induce structural stability and changes in rigidity/flexibility related to the number of glycosylations in the structure. These structural changes are important for its biological activity as well as the correct interaction of ligands in the RBD and NTD regions. Additionally, we evidenced a roto-translation phenomenon in the interaction of the ligand with RBD in the absence of glycosylation, which disappears due to the influence of glycosylation and the convergence of metastable states in RBM. Similarly, glycosylations in NTD promote an induced-fit phenomenon, which is not observed in the absence of glycosylations; this process is decisive for the activity of the ligand at the cryptic site. Altogether, these results provide an explanation of glycosylation relevance in biophysical properties and drug recognition to S protein of SARS-CoV-2 which must be considered in the rational drug development and virtual screening targeting S protein. |
| format | Preprint |
| id | oai:cris.upeu.edu.pe:20.500.15037/557 |
| institution | UPeU |
| language | English |
| publishDate | 2021 |
| publishDateRange | 2021 |
| publishDateSort | 2021 |
| record_format | dspace |
| spelling | oai:cris.upeu.edu.pe:20.500.15037/5572026-10-30T16:14:41ZGlycosylation as a key for enhancing drug recognition into spike glycoprotein of SARS-CoV-2Georcki Ropón‐PalaciosJhon Pérez-SilvaRicardo Rojas-HumpireGustavo E. Olivos-RamírezManuel Enrique Chenet ZutaVíctor VillanuevaSheyla Carmen-SifuentesKewin OtazuYaritza L. Ramirez-DíazIhosvany CampsGlycosylationGlycoproteinComputational biologyDrugBiologyProtein foldingChemistryCell biologyVirologyGeneticsPharmacologyGlycosylationGlycoproteinComputational biologyDrugBiologyProtein foldingChemistryCell biologyVirologyGeneticsPharmacologyHealth Sciences Medicine Infectious Diseases SARS-CoV-2 and COVID-19 ResearchLife Sciences Biochemistry, Genetics and Molecular Biology Molecular Biology vaccines and immunoinformatics approachesHealth Sciences Medicine Radiology, Nuclear Medicine and Imaging Monoclonal and Polyclonal Antibodies ResearchThe emergence of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and its spread since 2019 represents the major public health problem worldwide nowadays, generating a high number of infections and deaths. That’s why, in addition to vaccination campaigns, the design of a drug to help in the treatment of severe cases of COVID-19 is being investigated. In relation to SARS-CoV-2, one of its most studied proteins is the spike protein (S protein), which mediates host-cell entry and is heavily glycosylated. Regarding the latter, several investigations have been carried out, since it plays an important role in the evasion of the host's immune system and contributes to protein folding and the thermostability of the viral particle. For that reason, our objective was to evaluate the impact of glycosylations on the drug recognition on two domains of the S protein, the receptor-binding domain (RBD) and the N-terminal domain (NTD) through molecular dynamics simulations and computational biophysics analysis. Our results show that glycosylations in the S protein induce structural stability and changes in rigidity/flexibility related to the number of glycosylations in the structure. These structural changes are important for its biological activity as well as the correct interaction of ligands in the RBD and NTD regions. Additionally, we evidenced a roto-translation phenomenon in the interaction of the ligand with RBD in the absence of glycosylation, which disappears due to the influence of glycosylation and the convergence of metastable states in RBM. Similarly, glycosylations in NTD promote an induced-fit phenomenon, which is not observed in the absence of glycosylations; this process is decisive for the activity of the ligand at the cryptic site. Altogether, these results provide an explanation of glycosylation relevance in biophysical properties and drug recognition to S protein of SARS-CoV-2 which must be considered in the rational drug development and virtual screening targeting S protein.Preprinthttps://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/61af898d25f39a393dd040b4/original/glycosylation-as-a-key-for-enhancing-drug-recognition-into-spike-glycoprotein-of-sars-co-v-2.pdfhttps://doi.org/10.26434/chemrxiv-2021-gq85t10.26434/chemrxiv-2021-gq85thttps://hdl.handle.net/20.500.15037/557W4200357660en2573-22932021-12-082026-06-13T08:17:16Z2026-06-13T08:17:16Z |
| spellingShingle | Glycosylation Glycoprotein Computational biology Drug Biology Protein folding Chemistry Cell biology Virology Genetics Pharmacology Glycosylation Glycoprotein Computational biology Drug Biology Protein folding Chemistry Cell biology Virology Genetics Pharmacology Health Sciences Medicine Infectious Diseases SARS-CoV-2 and COVID-19 Research Life Sciences Biochemistry, Genetics and Molecular Biology Molecular Biology vaccines and immunoinformatics approaches Health Sciences Medicine Radiology, Nuclear Medicine and Imaging Monoclonal and Polyclonal Antibodies Research Georcki Ropón‐Palacios Jhon Pérez-Silva Ricardo Rojas-Humpire Gustavo E. Olivos-Ramírez Manuel Enrique Chenet Zuta Víctor Villanueva Sheyla Carmen-Sifuentes Kewin Otazu Yaritza L. Ramirez-Díaz Ihosvany Camps Glycosylation as a key for enhancing drug recognition into spike glycoprotein of SARS-CoV-2 |
| title | Glycosylation as a key for enhancing drug recognition into spike glycoprotein of SARS-CoV-2 |
| title_full | Glycosylation as a key for enhancing drug recognition into spike glycoprotein of SARS-CoV-2 |
| title_fullStr | Glycosylation as a key for enhancing drug recognition into spike glycoprotein of SARS-CoV-2 |
| title_full_unstemmed | Glycosylation as a key for enhancing drug recognition into spike glycoprotein of SARS-CoV-2 |
| title_short | Glycosylation as a key for enhancing drug recognition into spike glycoprotein of SARS-CoV-2 |
| title_sort | glycosylation as a key for enhancing drug recognition into spike glycoprotein of sars cov 2 |
| topic | Glycosylation Glycoprotein Computational biology Drug Biology Protein folding Chemistry Cell biology Virology Genetics Pharmacology Glycosylation Glycoprotein Computational biology Drug Biology Protein folding Chemistry Cell biology Virology Genetics Pharmacology Health Sciences Medicine Infectious Diseases SARS-CoV-2 and COVID-19 Research Life Sciences Biochemistry, Genetics and Molecular Biology Molecular Biology vaccines and immunoinformatics approaches Health Sciences Medicine Radiology, Nuclear Medicine and Imaging Monoclonal and Polyclonal Antibodies Research |
| topic_facet | Glycosylation Glycoprotein Computational biology Drug Biology Protein folding Chemistry Cell biology Virology Genetics Pharmacology Glycosylation Glycoprotein Computational biology Drug Biology Protein folding Chemistry Cell biology Virology Genetics Pharmacology Health Sciences Medicine Infectious Diseases SARS-CoV-2 and COVID-19 Research Life Sciences Biochemistry, Genetics and Molecular Biology Molecular Biology vaccines and immunoinformatics approaches Health Sciences Medicine Radiology, Nuclear Medicine and Imaging Monoclonal and Polyclonal Antibodies Research |
| url | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/61af898d25f39a393dd040b4/original/glycosylation-as-a-key-for-enhancing-drug-recognition-into-spike-glycoprotein-of-sars-co-v-2.pdf https://doi.org/10.26434/chemrxiv-2021-gq85t https://hdl.handle.net/20.500.15037/557 |
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