Characterization of the RNA-dependent RNA polymerase from Chikungunya virus and discovery of a novel ligand as a potential drug candidate
© 2022. The Author(s)..
Chikungunya virus (CHIKV) is the causative agent of Chikungunya fever, an acute febrile and arthritogenic illness with no effective treatments available. The development of effective therapeutic strategies could be significantly accelerated with detailed knowledge of the molecular components behind CHIKV replication. However, drug discovery is hindered by our incomplete understanding of their main components. The RNA-dependent RNA-polymerase (nsP4-CHIKV) is considered the key enzyme of the CHIKV replication complex and a suitable target for antiviral therapy. Herein, the nsP4-CHIKV was extensively characterized through experimental and computational biophysical methods. In the search for new molecules against CHIKV, a compound designated LabMol-309 was identified as a strong ligand of the nsp4-CHIKV and mapped to bind to its active site. The antiviral activity of LabMol-309 was evaluated in cellular-based assays using a CHIKV replicon system and a reporter virus. In conclusion, this study highlights the biophysical features of nsP4-CHIKV and identifies a new compound as a promising antiviral agent against CHIKV infection.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:12 |
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| Enthalten in: |
Scientific reports - 12(2022), 1 vom: 22. Juni, Seite 10601 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Freire, Marjorie C L C [VerfasserIn] |
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| Links: |
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| Themen: |
63231-63-0 |
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| Anmerkungen: |
Date Completed 24.06.2022 Date Revised 14.11.2022 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1038/s41598-022-14790-x |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM34253842X |
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| 100 | 1 | |a Freire, Marjorie C L C |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Characterization of the RNA-dependent RNA polymerase from Chikungunya virus and discovery of a novel ligand as a potential drug candidate |
| 264 | 1 | |c 2022 | |
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| 500 | |a Date Revised 14.11.2022 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2022. The Author(s). | ||
| 520 | |a Chikungunya virus (CHIKV) is the causative agent of Chikungunya fever, an acute febrile and arthritogenic illness with no effective treatments available. The development of effective therapeutic strategies could be significantly accelerated with detailed knowledge of the molecular components behind CHIKV replication. However, drug discovery is hindered by our incomplete understanding of their main components. The RNA-dependent RNA-polymerase (nsP4-CHIKV) is considered the key enzyme of the CHIKV replication complex and a suitable target for antiviral therapy. Herein, the nsP4-CHIKV was extensively characterized through experimental and computational biophysical methods. In the search for new molecules against CHIKV, a compound designated LabMol-309 was identified as a strong ligand of the nsp4-CHIKV and mapped to bind to its active site. The antiviral activity of LabMol-309 was evaluated in cellular-based assays using a CHIKV replicon system and a reporter virus. In conclusion, this study highlights the biophysical features of nsP4-CHIKV and identifies a new compound as a promising antiviral agent against CHIKV infection | ||
| 650 | 4 | |a Journal Article | |
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| 700 | 1 | |a Basso, Luis G M |e verfasserin |4 aut | |
| 700 | 1 | |a Mendes, Luis F S |e verfasserin |4 aut | |
| 700 | 1 | |a Mesquita, Nathalya C M R |e verfasserin |4 aut | |
| 700 | 1 | |a Mottin, Melina |e verfasserin |4 aut | |
| 700 | 1 | |a Fernandes, Rafaela S |e verfasserin |4 aut | |
| 700 | 1 | |a Policastro, Lucca R |e verfasserin |4 aut | |
| 700 | 1 | |a Godoy, Andre S |e verfasserin |4 aut | |
| 700 | 1 | |a Santos, Igor A |e verfasserin |4 aut | |
| 700 | 1 | |a Ruiz, Uriel E A |e verfasserin |4 aut | |
| 700 | 1 | |a Caruso, Icaro P |e verfasserin |4 aut | |
| 700 | 1 | |a Sousa, Bruna K P |e verfasserin |4 aut | |
| 700 | 1 | |a Jardim, Ana C G |e verfasserin |4 aut | |
| 700 | 1 | |a Almeida, Fabio C L |e verfasserin |4 aut | |
| 700 | 1 | |a Gil, Laura H V G |e verfasserin |4 aut | |
| 700 | 1 | |a Andrade, Carolina H |e verfasserin |4 aut | |
| 700 | 1 | |a Oliva, Glaucius |e verfasserin |4 aut | |
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