TY - JOUR
T1 - Nasal delivery of single-domain antibody improves symptoms of SARS-CoV-2 infection in an animal model
AU - Haga, Kei
AU - Takai-Todaka, Reiko
AU - Matsumura, Yuta
AU - Song, Chihong
AU - Takano, Tomomi
AU - Tojo, Takuto
AU - Nagami, Atsushi
AU - Ishida, Yuki
AU - Masaki, Hidekazu
AU - Tsuchiya, Masayuki
AU - Ebisudani, Toshiki
AU - Sugimoto, Shinya
AU - Sato, Toshiro
AU - Yasuda, Hiroyuki
AU - Fukunaga, Koichi
AU - Sawada, Akihito
AU - Nemoto, Naoto
AU - Murata, Kazuyoshi
AU - Morimoto, Takuya
AU - Katayama, Kazuhiko
N1 - Publisher Copyright:
© 2021 Haga et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2021/10
Y1 - 2021/10
N2 - The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes the disease COVID-19 can lead to serious symptoms, such as severe pneumonia, in the elderly and those with underlying medical conditions. While vaccines are now available, they do not work for everyone and therapeutic drugs are still needed, particularly for treating life-threatening conditions. Here, we showed nasal delivery of a new, unmodified camelid single-domain antibody (VHH), termed K-874A, effectively inhibited SARS-CoV-2 titers in infected lungs of Syrian hamsters without causing weight loss and cytokine induction. In vitro studies demonstrated that K-874A neutralized SARS-CoV-2 in both VeroE6/TMPRSS2 and human lung-derived alveolar organoid cells. Unlike other drug candidates, K-874A blocks viral membrane fusion rather than viral attachment. Cryo-electron microscopy revealed K-874A bound between the receptor binding domain and N-terminal domain of the virus S protein. Further, infected cells treated with K-874A produced fewer virus progeny that were less infective. We propose that direct administration of K-874A to the lung could be a new treatment for preventing the reinfection of amplified virus in COVID-19 patients.
AB - The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes the disease COVID-19 can lead to serious symptoms, such as severe pneumonia, in the elderly and those with underlying medical conditions. While vaccines are now available, they do not work for everyone and therapeutic drugs are still needed, particularly for treating life-threatening conditions. Here, we showed nasal delivery of a new, unmodified camelid single-domain antibody (VHH), termed K-874A, effectively inhibited SARS-CoV-2 titers in infected lungs of Syrian hamsters without causing weight loss and cytokine induction. In vitro studies demonstrated that K-874A neutralized SARS-CoV-2 in both VeroE6/TMPRSS2 and human lung-derived alveolar organoid cells. Unlike other drug candidates, K-874A blocks viral membrane fusion rather than viral attachment. Cryo-electron microscopy revealed K-874A bound between the receptor binding domain and N-terminal domain of the virus S protein. Further, infected cells treated with K-874A produced fewer virus progeny that were less infective. We propose that direct administration of K-874A to the lung could be a new treatment for preventing the reinfection of amplified virus in COVID-19 patients.
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U2 - 10.1371/journal.ppat.1009542
DO - 10.1371/journal.ppat.1009542
M3 - Article
C2 - 34648602
AN - SCOPUS:85117575219
SN - 1553-7366
VL - 17
JO - PLoS Pathogens
JF - PLoS Pathogens
IS - 10
M1 - e1009542
ER -
