In silico designed Axl receptor blocking drug candidates against Zika virus infection
Please always quote using this URN: urn:nbn:de:bvb:20-opus-176739
- After a large outbreak in Brazil, novel drugs against Zika virus became extremely necessary. Evaluation of virus-based pharmacological strategies concerning essential host factors brought us to the idea that targeting the Axl receptor by blocking its dimerization function could be critical for virus entry. Starting from experimentally validated compounds, such as RU-301, RU-302, warfarin, and R428, we identified a novel compound 2′ (R428 derivative) to be the most potent for this task amongst a number of alternative compounds and leads. TheAfter a large outbreak in Brazil, novel drugs against Zika virus became extremely necessary. Evaluation of virus-based pharmacological strategies concerning essential host factors brought us to the idea that targeting the Axl receptor by blocking its dimerization function could be critical for virus entry. Starting from experimentally validated compounds, such as RU-301, RU-302, warfarin, and R428, we identified a novel compound 2′ (R428 derivative) to be the most potent for this task amongst a number of alternative compounds and leads. The improved affinity of compound 2′ was confirmed by molecular docking as well as molecular dynamics simulation techniques using implicit solvation models. The current study summarizes a new possibility for inhibition of the Axl function as a potential target for future antiviral therapies.…
Author: | Edita Sarukhanyan, Sergey Shityakov, Thomas DandekarORCiD |
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URN: | urn:nbn:de:bvb:20-opus-176739 |
Document Type: | Journal article |
Faculties: | Medizinische Fakultät / Klinik und Poliklinik für Anästhesiologie (ab 2004) |
Fakultät für Biologie / Theodor-Boveri-Institut für Biowissenschaften | |
Language: | English |
Parent Title (English): | ACS Omega |
Year of Completion: | 2018 |
Volume: | 3 |
Issue: | 5 |
Pagenumber: | 5281-5290 |
Source: | ACS Omega 2018, 3(5), 5281-5290. DOI: 10.1021/acsomega.8b00223 |
DOI: | https://doi.org/10.1021/acsomega.8b00223 |
Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 615 Pharmakologie, Therapeutik |
Tag: | Zika virus; free energy; molecular docking; molecular dynamics; pharmacology; proteins; simulation; structure-activity relationship; viruses |
Release Date: | 2019/02/26 |
Collections: | Open-Access-Publikationsfonds / Förderzeitraum 2018 |
Licence (German): | CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International |