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 ... -  《-》

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 ... -  《-》

Neutralization of SARS-CoV-2 by Destruction of the Prefusion Spike.

There are as yet no licensed therapeutics for the COVID-19 pandemic. The causal coronavirus (SARS-CoV-2) binds host cells via a trimeric spike whose receptor binding domain (RBD) recognizes angiotensin-converting enzyme 2, initiating conformational changes that drive membrane fusion. We find that the monoclonal antibody CR3022 binds the RBD tightly, neutralizing SARS-CoV-2, and report the crystal structure at 2.4 Å of the Fab/RBD complex. Some crystals are suitable for screening for entry-blocking inhibitors. The highly conserved, structure-stabilizing CR3022 epitope is inaccessible in the prefusion spike, suggesting that CR3022 binding facilitates conversion to the fusion-incompetent post-fusion state. Cryogenic electron microscopy (cryo-EM) analysis confirms that incubation of spike with CR3022 Fab leads to destruction of the prefusion trimer. Presentation of this cryptic epitope in an RBD-based vaccine might advantageously focus immune responses. Binders at this epitope could be useful therapeutically, possibly in synergy with an antibody that blocks receptor attachment.

Huo J ，Zhao Y ，Ren J ，Zhou D ，Duyvesteyn HME ，Ginn HM ，Carrique L ，Malinauskas T ，Ruza RR ，Shah PNM ，Tan TK ，Rijal P ，Coombes N ，Bewley KR ，Tree JA ，Radecke J ，Paterson NG ，Supasa P ，Mongkolsapaya J ，Screaton GR ，Carroll M ，Townsend A ，Fry EE ，Owens RJ ，Stuart DI ... -  《-》

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 ... -  《-》

Neutralizing nanobodies bind SARS-CoV-2 spike RBD and block interaction with ACE2.

Huo J ，Le Bas A ，Ruza RR ，Duyvesteyn HME ，Mikolajek H ，Malinauskas T ，Tan TK ，Rijal P ，Dumoux M ，Ward PN ，Ren J ，Zhou D ，Harrison PJ ，Weckener M ，Clare DK ，Vogirala VK ，Radecke J ，Moynié L ，Zhao Y ，Gilbert-Jaramillo J ，Knight ML ，Tree JA ，Buttigieg KR ，Coombes N ，Elmore MJ ，Carroll MW ，Carrique L ，Shah PNM ，James W ，Townsend AR ，Stuart DI ，Owens RJ ，Naismith JH ... -  《-》