Two pan-SARS-CoV-2 nanobodies and their multivalent derivatives effectively prevent Omicron infections in mice.
Cell Rep Med
; 4(2): 100918, 2023 02 21.
Статья
в английский
| MEDLINE | ID: covidwho-2184477
ABSTRACT
With the widespread vaccinations against coronavirus disease 2019 (COVID-19), we are witnessing gradually waning neutralizing antibodies and increasing cases of breakthrough infections, necessitating the development of drugs aside from vaccines, particularly ones that can be administered outside of hospitals. Here, we present two cross-reactive nanobodies (R14 and S43) and their multivalent derivatives, including decameric ones (fused to the immunoglobulin M [IgM] Fc) that maintain potent neutralizing activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) after aerosolization and display not only pan-SARS-CoV-2 but also varied pan-sarbecovirus activities. Through respiratory administration to mice, monovalent and decameric R14 significantly reduce the lung viral RNAs at low dose and display potent pre- and post-exposure protection. Furthermore, structural studies reveal the neutralizing mechanisms of R14 and S43 and the multiple inhibition effects that the multivalent derivatives exert. Our work demonstrates promising convenient drug candidates via respiratory administration against SARS-CoV-2 infection, which can contribute to containing the COVID-19 pandemic.
ключевые слова
Полный текст:
Имеется в наличии
Коллекция:
Международные базы данных
база данных:
MEDLINE
Основная тема:
Single-Domain Antibodies
/
COVID-19
Тип исследования:
Экспериментальные исследования
/
Рандомизированные контролируемые испытания
Темы:
Вакцина
/
Варианты
Пределы темы:
Животные
/
Люди
Язык:
английский
Журнал:
Cell Rep Med
Год:
2023
Тип:
Статья
Аффилированная страна:
J.xcrm.2023.100918
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