Angewandte Chemie (International ed. in English) · 2022

Comprehensive Fragment Screening of the SARS-CoV-2 Proteome Explores Novel Chemical Space for Drug Development.

СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди

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Berg Hannes, Wirtz Martin Maria A, Altincekic Nadide, Alshamleh Islam, Kaur Bains Jasleen, Blechar Julius, Ceylan Betül, de Jesus Vanessa, Dhamotharan Karthikeyan, Fuks Christin, Gande Santosh L, Hargittay Bruno, Hohmann Katharina F, Hutchison Marie T, Marianne Korn Sophie, Krishnathas Robin, Kutz Felicitas, Linhard Verena, Matzel Tobias, Meiser Nathalie, Niesteruk Anna, Pyper Dennis J, Schulte Linda, Trucks Sven, Azzaoui Kamal, Blommers Marcel J J, Gadiya Yojana, Karki Reagon, Zaliani Andrea, Gribbon Philip, da Silva Almeida Marcius, Dinis Anobom Cristiane, Bula Anna L, Bütikofer Matthias, Putinhon Caruso Ícaro, Caterina Felli Isabella, Da Poian Andrea T, Cardoso de Amorim Gisele, Fourkiotis Nikolaos K, Gallo Angelo, Ghosh Dhiman, Gomes-Neto Francisco, Gorbatyuk Oksana, Hao Bing, Kurauskas Vilius, Lecoq Lauriane, Li Yunfeng, Cunha Mebus-Antunes Nathane, Mompeán Miguel, Cristtina Neves-Martins Thais, Ninot-Pedrosa Martí, Pinheiro Anderson S, Pontoriero Letizia, Pustovalova Yulia, Riek Roland, Robertson Angus J, Jose Abi Saad Marie, Treviño Miguel Á, Tsika Aikaterini C, Almeida Fabio C L, Bax Ad, Henzler-Wildman Katherine, Hoch Jeffrey C, Jaudzems Kristaps, Laurents Douglas V, Orts Julien, Pierattelli Roberta, Spyroulias Georgios A, Duchardt-Ferner Elke, Ferner Jan, Fürtig Boris, Hengesbach Martin, Löhr Frank, Qureshi Nusrat, Richter Christian, Saxena Krishna, Schlundt Andreas, Sreeramulu Sridhar, Wacker Anna, Weigand Julia E, Wirmer-Bartoschek Julia, Wöhnert Jens, Schwalbe Harald

Аннотация

SARS-CoV-2 (SCoV2) and its variants of concern pose serious challenges to the public health. The variants increased challenges to vaccines, thus necessitating for development of new intervention strategies including anti-virals. Within the international Covid19-NMR consortium, we have identified binders targeting the RNA genome of SCoV2. We established protocols for the production and NMR characterization of more than 80 % of all SCoV2 proteins. Here, we performed an NMR screening using a fragment library for binding to 25 SCoV2 proteins and identified hits also against previously unexplored SCoV2 proteins. Computational mapping was used to predict binding sites and identify functional moieties (chemotypes) of the ligands occupying these pockets. Striking consensus was observed between NMR-detected binding sites of the main protease and the computational procedure. Our investigation provides novel structural and chemical space for structure-based drug design against the SCoV2 proteome.

Предметные рубрики MeSH

Humans SARS-CoV-2 Proteome Ligands Drug Design COVID-19 Drug Treatment

Comprehensive Fragment Screening of the SARS-CoV-2 Proteome Explores Novel Chemical Space for Drug Development.

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Аннотация

Предметные рубрики MeSH