MedElevator Войти в исследования
← Поиск публикаций

DOI 10.1038/s42003-023-05317-9

Медицинская библиотека · Communications biology · 2023

Calpeptin is a potent cathepsin inhibitor and drug candidate for SARS-CoV-2 infections.

Reinke Patrick Y A, de Souza Edmarcia Elisa, Günther Sebastian, Falke Sven, Lieske Julia, Ewert Wiebke, Loboda Jure, Herrmann Alexander, Rahmani Mashhour Aida, Karničar Katarina, Usenik Aleksandra, Lindič Nataša, Sekirnik Andreja, Botosso Viviane Fongaro, Santelli Gláucia Maria Machado, Kapronezai Josana, de Araújo Marcelo Valdemir, Silva-Pereira Taiana Tainá, Filho Antônio Francisco de Souza, Tavares Mariana Silva, Flórez-Álvarez Lizdany, de Oliveira Danielle Bruna Leal, Durigon Edison Luiz, Giaretta Paula Roberta, Heinemann Marcos Bryan, Hauser Maurice, Seychell Brandon, Böhler Hendrik, Rut Wioletta, Drag Marcin, Beck Tobias, Cox Russell, Chapman Henry N, Betzel Christian, Brehm Wolfgang, Hinrichs Winfried, Ebert Gregor, Latham Sharissa L, Guimarães Ana Marcia de Sá, Turk Dusan, Wrenger Carsten, Meents Alke

СтатьяПоддержка исследования: вне правительства СШАПеревод в очереди

Аннотация

Several drug screening campaigns identified Calpeptin as a drug candidate against SARS-CoV-2. Initially reported to target the viral main protease (Mpro), its moderate activity in Mpro inhibition assays hints at a second target. Indeed, we show that Calpeptin is an extremely potent cysteine cathepsin inhibitor, a finding additionally supported by X-ray crystallography. Cell infection assays proved Calpeptin's efficacy against SARS-CoV-2. Treatment of SARS-CoV-2-infected Golden Syrian hamsters with sulfonated Calpeptin at a dose of 1 mg/kg body weight reduces the viral load in the trachea. Despite a higher risk of side effects, an intrinsic advantage in targeting host proteins is their mutational stability in contrast to highly mutable viral targets. Here we show that the inhibition of cathepsins, a protein family of the host organism, by calpeptin is a promising approach for the treatment of SARS-CoV-2 and potentially other viral infections.

Для цитирования: Reinke Patrick Y A, de Souza Edmarcia Elisa, Günther Sebastian, Falke Sven, Lieske Julia, Ewert Wiebke, Loboda Jure, Herrmann Alexander, Rahmani Mashhour Aida, Karničar Katarina, Usenik Aleksandra, Lindič Nataša, Sekirnik Andreja, Botosso Viviane Fongaro, Santelli Gláucia Maria Machado, Kapronezai Josana, de Araújo Marcelo Valdemir, Silva-Pereira Taiana Tainá, Filho Antônio Francisco de Souza, Tavares Mariana Silva, Flórez-Álvarez Lizdany, de Oliveira Danielle Bruna Leal, Durigon Edison Luiz, Giaretta Paula Roberta, Heinemann Marcos Bryan, Hauser Maurice, Seychell Brandon, Böhler Hendrik, Rut Wioletta, Drag Marcin, Beck Tobias, Cox Russell, Chapman Henry N, Betzel Christian, Brehm Wolfgang, Hinrichs Winfried, Ebert Gregor, Latham Sharissa L, Guimarães Ana Marcia de Sá, Turk Dusan, Wrenger Carsten, Meents Alke. Calpeptin is a potent cathepsin inhibitor and drug candidate for SARS-CoV-2 infections.. Communications biology. 2023. DOI: 10.1038/s42003-023-05317-9.

Предметные рубрики MeSH

HumansCOVID-19SARS-CoV-2CathepsinsAntiviral AgentsProtease InhibitorsCysteine EndopeptidasesDipeptides
Подготовка и перевод публикации
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…

История · было → стало

Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.

Тип публикации указан по данным источника. Уровень доказательности автоматически не присваивается.