In-silico homology assisted identification of inhibitor of RNA binding against 2019-nCoV N-protein (N terminal domain)
The N terminal domain (NTD) of Nucleocapsid protein (N protein) of coronavirus (CoV) binds to the viral (+) sense RNA and results in CoV ribonucleoprotien (CoV RNP) complex, essential for the virus replication. In this study, the RNA-binding N terminal domain (NTD) of the N protein was targeted for the identification of possible inhibitors of RNA binding. Two NTD structures of N proteins were selected (2OFZ and 1SSK, 92% homology) for virtual screening of 56,079 compounds from Asinex and Maybridge library to identify top 15 hits for each of the targets based on 'docking score'. These top-hits were further screened for MM-GBSA binding free energy, pharmacokinetic properties (QikProp) and drug-likeness (SwissADME) and subjected to molecular dynamics (MD) studies. Two suitable binders (ZINC00003118440 and ZINC0000146942) against the target 2OFZ were identified. ZINC00003118440 is a theophylline derivative under the drug class 'bronchodilators' and further screening with approved bronchodilators was also studied to identify their ability to bind to the RNA binding region on the N protein. The other identified top hit is ZINC0000146942, which is a 3,4dihydropyrimidone class molecule. Hence this study suggests two important class of compounds, theophylline and pyrimidone derivaties as possible inhibitors of RNA binding to the N terminal domain of N protein of coronavirus, thus opening new avenues for in vitro validations. Communicated by Ramaswamy H. Sarma.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:39 |
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| Enthalten in: |
Journal of biomolecular structure & dynamics - 39(2021), 8 vom: 01. Mai, Seite 2724-2732 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Sarma, Phulen [VerfasserIn] |
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| Links: |
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| Themen: |
2019 novel corona virus |
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| Anmerkungen: |
Date Completed 18.06.2021 Date Revised 18.06.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1080/07391102.2020.1753580 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM308521188 |
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| 245 | 1 | 0 | |a In-silico homology assisted identification of inhibitor of RNA binding against 2019-nCoV N-protein (N terminal domain) |
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| 520 | |a The N terminal domain (NTD) of Nucleocapsid protein (N protein) of coronavirus (CoV) binds to the viral (+) sense RNA and results in CoV ribonucleoprotien (CoV RNP) complex, essential for the virus replication. In this study, the RNA-binding N terminal domain (NTD) of the N protein was targeted for the identification of possible inhibitors of RNA binding. Two NTD structures of N proteins were selected (2OFZ and 1SSK, 92% homology) for virtual screening of 56,079 compounds from Asinex and Maybridge library to identify top 15 hits for each of the targets based on 'docking score'. These top-hits were further screened for MM-GBSA binding free energy, pharmacokinetic properties (QikProp) and drug-likeness (SwissADME) and subjected to molecular dynamics (MD) studies. Two suitable binders (ZINC00003118440 and ZINC0000146942) against the target 2OFZ were identified. ZINC00003118440 is a theophylline derivative under the drug class 'bronchodilators' and further screening with approved bronchodilators was also studied to identify their ability to bind to the RNA binding region on the N protein. The other identified top hit is ZINC0000146942, which is a 3,4dihydropyrimidone class molecule. Hence this study suggests two important class of compounds, theophylline and pyrimidone derivaties as possible inhibitors of RNA binding to the N terminal domain of N protein of coronavirus, thus opening new avenues for in vitro validations. Communicated by Ramaswamy H. Sarma | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a N terminal domain | |
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| 650 | 4 | |a RNA binding | |
| 650 | 4 | |a SARS-CoV-2 | |
| 650 | 4 | |a drug design | |
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| 700 | 1 | |a Shekhar, Nishant |e verfasserin |4 aut | |
| 700 | 1 | |a Prajapat, Manisha |e verfasserin |4 aut | |
| 700 | 1 | |a Avti, Pramod |e verfasserin |4 aut | |
| 700 | 1 | |a Kaur, Hardeep |e verfasserin |4 aut | |
| 700 | 1 | |a Kumar, Subodh |e verfasserin |4 aut | |
| 700 | 1 | |a Singh, Sanjay |e verfasserin |4 aut | |
| 700 | 1 | |a Kumar, Harish |e verfasserin |4 aut | |
| 700 | 1 | |a Prakash, Ajay |e verfasserin |4 aut | |
| 700 | 1 | |a Dhibar, Deba Prasad |e verfasserin |4 aut | |
| 700 | 1 | |a Medhi, Bikash |e verfasserin |4 aut | |
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