Sisi Shan's research while affiliated with Tsinghua University and other places

... With the rapid global spread of Omicron and other notable variants, the development of more potent antibodies has been a global concern. Effective nanobodies have been successfully generated in biological experiments [1,2] , which could be used for targeting the SARS-CoV-2 virus for the diagnosis and treatment of COVID-19. However ， there is a lack of in silico screening techniques to promptly identify a large number of nanobodies. ...

... In contrast, TH132 and TH281 show a broad spectrum of neutralizing activity against all Omicron sublineages. Recently, several antibodies, such as F61 29 and CAB-A17 30 from the IGHV3-66/53 germline, were also reported to show broadly potent neutralizing activity across variants. We further analyzed the amino acid sequence alignment of TH281 and TH132 with other previously reported IGHV3-66/53 antibodies (Fig. S9c) and found that several residue differences play critical roles in the cross-reactivity against different VOCs. ...

... The large number of mutations (15 mutations in BA.1 RBD) in Omicron variants abolished the binding of nanobody mNb6 and thus the cross-linking between mNb6(108FFY) and Omicron RBD (Figure S9). We therefore used a different nanobody Nb70 capable of binding with Omicron J o u r n a l P r e -p r o o f variants, contacting two RBDs in their up-state38 . We decided to incorporate FSY at site G56, Y103, or D115 of nanobody Nb70 based on the crystal structure38 to target the K386, Y369, or K378 of the Spike RBD, respectively (Figure S10A). ...

... GeoPPI [103] proposed a graph neural network-based autoencoder to extract structural embedding at the protein-protein binding interface. The subsequent downstream models allow accurate predictions for protein-protein binding affinity upon mutations [103] and further design effective antibody against SARS-CoV-2 variants [104]. GRACE has been applied to learn geometric representation of protein structures [105]. ...

... The identification of epitopes recognized by antibodies from vaccinated subjects involved in virus neutralization is crucial not only for understanding the mechanism of the action of existing vaccines but also for the development of refined active vaccination and passive immunization strategies against COVID-19 [11,12]. Most of the current vaccines are focused on obtaining an S-specific antibody response with special attention to RBD-specific antibody response, because it has been seen that RBD-specific antibodies are correlated with high neutralizing activity against SARS-CoV-2 [13][14][15]. However, the number of mutations acquired by each new variant of concern (VOC), indicates the importance of identifying epitopes conserved among VOCs targeted by neutralizing antibodies which are located not only in RBD but also outside of RBD [16]. ...

... Compared to the soluble gp350 vaccine, focusing on the presentation of the CR-2 binding domain of gp350 on nanoparticles induced 10-100 fold higher neutralizing antibodies in mice [47]. Other approaches for targeting EBV have explored the use of EBV-specific T-cells or EBV-specific antibodies [15,48,49]. More recently, it was reported that a VLP vaccine incorporating five EBV glycoproteins, gp350, gB, gp42, gH, and gL, could elicit high titer of antibodies against EBV in rabbits [50]. ...

... The comparison of P4A2 with other known broadly neutralizing antibodies shows that epitopes of 87G7, 510A5, Cov2-2196, NCV2SG48, NCV2SG53, S2E12, S2K146 and ZWD12 show varying degrees of overlap with that of P4A2. Among these mAbs, P4A2 is the only one that forms multiple interactions with its cognate epitope on Spike-RBD which is composed of residues that are critical for interaction with ACE2 [8][9][10][11][12][13][14][15][16][17][18][19][20][21] (S11 Fig and S2 Table). Overall, our data suggests that P4A2 may represent an viable therapeutic option which is required to reduce the impact of the COVID19 pandemic on human health across the globe. ...

... This stringent grouping of Abs and Nbs, based on high similarity score of their respective ES, may prove a useful adjunct in structure prediction based on amino acid sequence and antibody competition. Previous work identified the over-represented public class of mAbs encoded by IGHV3-53 and IGHV3-66 that neutralize the spike 45,49,50 . We also investigated the V(D)J gene combinations representing those mAb structures ( Supplementary Fig. 6a). ...

... This can be accelerated by a highly automated mobile laboratory for on-site rapid diagnosis [133] . Rapid diagnostic tests based on clustered regularly interspaced short palindromic repeats can also detect the virus within 15 minutes with minimal hands-on time [134] . ...

... ; https://doi.org/10.1101/2023.08.12.553079 doi: bioRxiv preprint based on protein data bank (PDB) ID 6VXX. 17 The protein is a functional trimer, with one of them shown in green and yellow color, while the other two are colored in gray. The receptor binding region (corresponds to the entries marked by * in Table 1), and subunits S1 and S2 are marked. ...