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タイトル	Nanobody cocktails potently neutralize SARS-CoV-2 D614G N501Y variant and protect mice.
ジャーナル・号・ページ	Proc Natl Acad Sci U S A, Vol. 118, Issue 19, Year 2021
掲載日	2021年5月11日
著者	Phillip Pymm / Amy Adair / Li-Jin Chan / James P Cooney / Francesca L Mordant / Cody C Allison / Ester Lopez / Ebene R Haycroft / Matthew T O'Neill / Li Lynn Tan / Melanie H Dietrich / Damien Drew / Marcel Doerflinger / Michael A Dengler / Nichollas E Scott / Adam K Wheatley / Nicholas A Gherardin / Hariprasad Venugopal / Deborah Cromer / Miles P Davenport / Raelene Pickering / Dale I Godfrey / Damian F J Purcell / Stephen J Kent / Amy W Chung / Kanta Subbarao / Marc Pellegrini / Alisa Glukhova / Wai-Hong Tham /
PubMed 要旨	Neutralizing antibodies are important for immunity against SARS-CoV-2 and as therapeutics for the prevention and treatment of COVID-19. Here, we identified high-affinity nanobodies from alpacas ...Neutralizing antibodies are important for immunity against SARS-CoV-2 and as therapeutics for the prevention and treatment of COVID-19. Here, we identified high-affinity nanobodies from alpacas immunized with coronavirus spike and receptor-binding domains (RBD) that disrupted RBD engagement with the human receptor angiotensin-converting enzyme 2 (ACE2) and potently neutralized SARS-CoV-2. Epitope mapping, X-ray crystallography, and cryo-electron microscopy revealed two distinct antigenic sites and showed two neutralizing nanobodies from different epitope classes bound simultaneously to the spike trimer. Nanobody-Fc fusions of the four most potent nanobodies blocked ACE2 engagement with RBD variants present in human populations and potently neutralized both wild-type SARS-CoV-2 and the N501Y D614G variant at concentrations as low as 0.1 nM. Prophylactic administration of either single nanobody-Fc or as mixtures reduced viral loads by up to 10-fold in mice infected with the N501Y D614G SARS-CoV-2 virus. These results suggest a role for nanobody-Fc fusions as prophylactic agents against SARS-CoV-2.
リンク	Proc Natl Acad Sci U S A / PubMed:33893175 / PubMed Central
手法	EM (単粒子)
解像度	2.9 - 3.76 Å
構造データ	23566 7lx5 EMDB-23566, PDB-7lx5: The SARS-CoV-2 spike protein receptor binding domain bound to neutralizing nanobodies WNb 2 and WNb 10 手法: EM (単粒子) / 解像度: 3.44 Å EMDB-23567: Cryo-EM map of SARS-CoV-2 Spike protein bound to neutralising nanobodies WNb2 and WNb10 (C3 symmetry) 手法: EM (単粒子) / 解像度: 2.9 Å EMDB-23568: Cryo-EM map of SARS-CoV-2 Spike protein in complex with neutralising nanobodies WNb2 and WNb10 (C1 symmetry) 手法: EM (単粒子) / 解像度: 3.76 Å
由来	severe acute respiratory syndrome coronavirus 2 (ウイルス) vicugna pacos (アルパカ) evere acute respiratory syndrome coronavirus 2 (ウイルス)
キーワード	VIRAL PROTEIN / SARS-CoV-2 / nanobody cocktail / coronavirus spike / neutralizing nanobody