Nanobody cocktails potently neutralize SARS-CoV-2 D614G N501Y variant and protect mice
Phillip Pymm, Amy Adair, Li‐Jin Chan, James P. Cooney, Francesca L. Mordant, Cody C. Allison, Ester López, Ebene R. Haycroft, Matthew T. O’Neill, Li Lynn Tan, Melanie H. Dietrich, Damien R. Drew, Marcel Doerflinger, Michael A. Dengler, Nichollas E. Scott, Adam K. Wheatley, Nicholas A. Gherardin, Hariprasad Venugopal, Deborah Cromer, Miles P. Davenport, R. J. Pickering, Dale I. Godfrey, Damian F. J. Purcell, Stephen J. Kent, Amy W. Chung, Kanta Subbarao, Marc Pellegrini, Alisa Glukhova, Wai‐Hong Tham
Abstract
Significance Neutralizing antibodies are important for immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and as therapeutics for the prevention and treatment of COVID-19. We identified high-affinity nanobodies against SARS-CoV-2 receptor-binding domain and found that nanobody cocktails consisting of two noncompeting nanobodies were able to block ACE2 engagement with RBD variants present in human populations and potently neutralize both wild-type SARS-CoV-2 and the N501Y D614G variant at low concentrations. Prophylactic administration of nanobody cocktails reduced viral loads in mice infected with the N501Y D614G SARS-CoV-2 virus, showing that nanobody cocktails are useful as prophylactic agents against SARS-CoV-2.