A neutralizing human antibody binds to the N-terminal domain of the Spike protein of SARS-CoV-2.

Developing therapeutics against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could be guided by the distribution of epitopes, not only on the receptor binding domain (RBD) of the Spike (S) protein but also across the full Spike (S) protein. We isolated and characterized monoclonal antibodies (mAbs) from 10 convalescent COVID-19 patients. Three mAbs showed neutralizing activities against authentic SARS-CoV-2. One mAb, named 4A8, exhibits high neutralization potency against both authentic and pseudotyped SARS-CoV-2 but does not bind the RBD. We defined the epitope of 4A8 as the N-terminal domain (NTD) of the S protein by determining with cryo-eletron microscopy its structure in complex with the S protein to an overall resolution of 3.1 angstroms and local resolution of 3.3 angstroms for the 4A8-NTD interface. This points to the NTD as a promising target for therapeutic mAbs against COVID-19.

Chi X ，Yan R ，Zhang J ，Zhang G ，Zhang Y ，Hao M ，Zhang Z ，Fan P ，Dong Y ，Yang Y ，Chen Z ，Guo Y ，Zhang J ，Li Y ，Song X ，Chen Y ，Xia L ，Fu L ，Hou L ，Xu J ，Yu C ，Li J ，Zhou Q ，Chen W ... -  《-》

Cross-neutralization of SARS-CoV-2 by a human monoclonal SARS-CoV antibody.

Pinto D ，Park YJ ，Beltramello M ，Walls AC ，Tortorici MA ，Bianchi S ，Jaconi S ，Culap K ，Zatta F ，De Marco A ，Peter A ，Guarino B ，Spreafico R ，Cameroni E ，Case JB ，Chen RE ，Havenar-Daughton C ，Snell G ，Telenti A ，Virgin HW ，Lanzavecchia A ，Diamond MS ，Fink K ，Veesler D ，Corti D ... -  《-》

Potent neutralizing antibodies against multiple epitopes on SARS-CoV-2 spike.

Liu L ，Wang P ，Nair MS ，Yu J ，Rapp M ，Wang Q ，Luo Y ，Chan JF ，Sahi V ，Figueroa A ，Guo XV ，Cerutti G ，Bimela J ，Gorman J ，Zhou T ，Chen Z ，Yuen KY ，Kwong PD ，Sodroski JG ，Yin MT ，Sheng Z ，Huang Y ，Shapiro L ，Ho DD ... -  《-》

Targeting SARS-CoV2 Spike Protein Receptor Binding Domain by Therapeutic Antibodies.

As the number of people infected with the newly identified 2019 novel coronavirus (SARS-CoV2) is continuously increasing every day, development of potential therapeutic platforms is vital. Based on the comparatively high similarity of receptor-binding domain (RBD) in SARS-CoV2 and SARS-CoV, it seems crucial to assay the cross-reactivity of anti-SARS-CoV monoclonal antibodies (mAbs) with SARS-CoV2 spike (S)-protein. Indeed, developing mAbs targeting SARS-CoV2 S-protein RBD could show novel applications for rapid and sensitive development of potential epitope-specific vaccines (ESV). Herein, we present an overview on the discovery of new CoV followed by some explanation on the SARS-CoV2 S-protein RBD site. Furthermore, we surveyed the novel therapeutic mAbs for targeting S-protein RBD such as S230, 80R, F26G18, F26G19, CR3014, CR3022, M396, and S230.15. Afterwards, the mechanism of interaction of RBD and different mAbs were explained and it was suggested that one of the SARS-CoV-specific human mAbs, namely CR3022, could show the highest binding affinity with SARS-CoV2 S-protein RBD. Finally, some ongoing challenges and future prospects for rapid and sensitive advancement of therapeutic mAbs targeting S-protein RBD were discussed. In conclusion, it may be proposed that this review may pave the way for recognition of RBD and different mAbs to develop potential therapeutic ESV.

Hussain A ，Hasan A ，Nejadi Babadaei MM ，Bloukh SH ，Chowdhury MEH ，Sharifi M ，Haghighat S ，Falahati M ... -  《-》

Analysis of a SARS-CoV-2-Infected Individual Reveals Development of Potent Neutralizing Antibodies with Limited Somatic Mutation.

Antibody responses develop following SARS-CoV-2 infection, but little is known about their epitope specificities, clonality, binding affinities, epitopes, and neutralizing activity. We isolated B cells specific for the SARS-CoV-2 envelope glycoprotein spike (S) from a COVID-19-infected subject 21 days after the onset of clinical disease. 45 S-specific monoclonal antibodies were generated. They had undergone minimal somatic mutation with limited clonal expansion, and three bound the receptor-binding domain (RBD). Two antibodies neutralized SARS-CoV-2. The most potent antibody bound the RBD and prevented binding to the ACE2 receptor, while the other bound outside the RBD. Thus, most anti-S antibodies that were generated in this patient during the first weeks of COVID-19 infection were non-neutralizing and target epitopes outside the RBD. Antibodies that disrupt the SARS-CoV-2 S-ACE2 interaction can potently neutralize the virus without undergoing extensive maturation. Such antibodies have potential preventive and/or therapeutic potential and can serve as templates for vaccine design.

Seydoux E ，Homad LJ ，MacCamy AJ ，Parks KR ，Hurlburt NK ，Jennewein MF ，Akins NR ，Stuart AB ，Wan YH ，Feng J ，Whaley RE ，Singh S ，Boeckh M ，Cohen KW ，McElrath MJ ，Englund JA ，Chu HY ，Pancera M ，McGuire AT ，Stamatatos L ... -  《-》