| Autor: |
Dorothée Bardiot, Laura Vangeel, Mohamed Koukni, Philippe Arzel, Marleen Zwaagstra, Heyrhyoung Lyoo, Patrick Wanningen, Shamshad Ahmad, Linlin Zhang, Xinyuanyuan Sun, Adrien Delpal, Cecilia Eydoux, Jean-Claude Guillemot, Eveline Lescrinier, Hugo Klaassen, Pieter Leyssen, Dirk Jochmans, Karolien Castermans, Rolf Hilgenfeld, Colin Robinson, Etienne Decroly, Bruno Canard, Eric J. Snijder, Martijn J. van Hemert, Frank van Kuppeveld, Patrick Chaltin, Johan Neyts, Steven De Jonghe, Arnaud Marchand |
| Jazyk: |
angličtina |
| Rok vydání: |
2022 |
| Předmět: |
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| Zdroj: |
Molecules, Vol 27, Iss 3, p 1052 (2022) |
| Druh dokumentu: |
article |
| ISSN: |
1420-3049 |
| DOI: |
10.3390/molecules27031052 |
| Popis: |
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, has led to a pandemic, that continues to be a huge public health burden. Despite the availability of vaccines, there is still a need for small-molecule antiviral drugs. In an effort to identify novel and drug-like hit matter that can be used for subsequent hit-to-lead optimization campaigns, we conducted a high-throughput screening of a 160 K compound library against SARS-CoV-2, yielding a 1-heteroaryl-2-alkoxyphenyl analog as a promising hit. Antiviral profiling revealed this compound was active against various beta-coronaviruses and preliminary mode-of-action experiments demonstrated that it interfered with viral entry. A systematic structure–activity relationship (SAR) study demonstrated that a 3- or 4-pyridyl moiety on the oxadiazole moiety is optimal, whereas the oxadiazole can be replaced by various other heteroaromatic cycles. In addition, the alkoxy group tolerates some structural diversity. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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