7FG2

Minor cryo-EM structure of S protein trimer of SARS-CoV2 with K-874A VHH, composite map

Summary for 7FG2

• Entry DOI: 10.2210/pdb7fg2/pdb
• EMDB information: 31572 31573 31574 31575 31576 31577 31578
• Descriptor: Spike glycoprotein, K-874A VHH (2 entities in total)
• Functional Keywords: antibody, protein binding
• Biological source: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV, SARS-CoV-2); More
• Total number of polymer chains: 2
• Total formula weight: 155660.15

Authors

Song, C.,Murata, K.,Katayama, K. (deposition date: 2021-07-25, release date: 2021-09-29, Last modification date: 2022-03-23)

Primary citation

Haga, K.,Takai-Todaka, R.,Matsumura, Y.,Song, C.,Takano, T.,Tojo, T.,Nagami, A.,Ishida, Y.,Masaki, H.,Tsuchiya, M.,Ebisudani, T.,Sugimoto, S.,Sato, T.,Yasuda, H.,Fukunaga, K.,Sawada, A.,Nemoto, N.,Murata, K.,Morimoto, T.,Katayama, K.
Nasal delivery of single-domain antibody improves symptoms of SARS-CoV-2 infection in an animal model.
Plos Pathog., 17:e1009542-e1009542, 2021

PubMed Abstract: 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.

PubMed: 34648602
DOI: 10.1371/journal.ppat.1009542

Experimental method

ELECTRON MICROSCOPY (4.4 Å)