+検索条件
-Structure paper
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 | EMDB-23566, PDB-7lx5: EMDB-23567: EMDB-23568: |
由来 |
|
キーワード | VIRAL PROTEIN / SARS-CoV-2 / nanobody cocktail / coronavirus spike / neutralizing nanobody |