Spike protein binding prediction with neutralizing antibodies of SARS-CoV-2

Park, Tamina; Lee, Sangyeop; Kim, Seil; Kim, Mi Jeong; Kim, Hong Gi; Jun, Sangmi; Kim, Kyung Sik; Kim, Bum Tae; Park, Edmond Changkyun; Park, Daeui

doi:10.1101/2020.02.22.951178

Cited by 36 publications

(43 citation statements)

References 48 publications

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“…For CR3022, a monoclonal antibody targeting a highly conserved cryptic epitope 15 , 14 out of 28 binding residues of SARS-CoV-2 RBD were located in ID sites. For F26G19, a mouse antibody, 11 out of 20 sites were located at ID sites, indicating there was likely a relatively high binding affinity to the RBD fragment 25 . However, for m396, an antibody with relatively low binding affinity to SARS-CoV-2 RBD, only 5 out of 22 binding residues were located at ID sites 24 .…”

Section: Resultsmentioning

confidence: 99%

“…The neutralising titre results (Figure 4F) suggest the ID sites have neutralising activities against SARS-CoV-2, although the ID sites in SARS-CoV were unlikely to be neutralising sites 20 . To further validate the ID sites, we compared the binding residues of the S protein to reported monoclonal antibodies with the ID sites of RBD 15,24,25 . Interestingly, some binding residues of SARS-CoV-2-specific neutralising antibodies were highly similar to the ID sites (Figure 5).…”

Section: Resultsmentioning

confidence: 99%

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Mapping the Immunodominance Landscape of SARS-CoV-2 Spike Protein for the Design of Vaccines against COVID-19

Zhang

Chen

et al. 2020

Preprint

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24The ongoing coronavirus disease 2019 pandemic is a serious threat to 25 global public health, and imposes severe burdens on the entire human society. The 26 severe acute respiratory syndrome (SARS) coronavirus-2 (SARS-CoV-2) can cause 27 severe respiratory illness and death. Currently, there are no specific antiviral drugs 28 that can treat COVID-19. Several vaccines against SARS-CoV-2 are being actively 29 developed by research groups around the world. The surface S (spike) protein and the 30 highly expressed internal N (nucleocapsid) protein of SARS-CoV-2 are widely 31 considered as promising candidates for vaccines. In order to guide the design of an 32 effective vaccine, we need experimental data on these potential epitope candidates. In 33 this study, we mapped the immunodominant (ID) sites of S protein using sera samples 34 collected from recently discharged COVID-19 patients. The SARS-CoV-2 S protein-35 specific antibody levels in the sera of recovered COVID-19 patients were strongly 36 correlated with the neutralising antibody titres. We used epitope mapping to 37 determine the landscape of ID sites of S protein, which identified nine linearized B 38 cell ID sites. Four out of the nine ID sites were found in the receptor-binding domain 39 (RBD). Further analysis showed that these ID sites are potential high-affinity SARS-40 CoV-2 antibody binding sites. Peptides containing two out of the nine sites were 41 tested as vaccine candidates against SARS-CoV-2 in a mouse model. We detected 42 epitope-specific antibodies and SARS-CoV-2-neutralising activity in the immunised 43 mice. This study for the first time provides human serological data for the design of 44 vaccines against COVID-19.45 46 47 The coronavirus disease 2019 (COVID-19), a novel infectious disease caused by 48 severe acute respiratory syndrome coronavirus 2, SARS-CoV-2, first emerged in 49 December 2019 and has since become a worldwide pandemic. COVID-19 infections 50 have so far led to over 2 million cases and more than 0.13 million deaths across more 51 than 200 countries and geographical regions around the world. The World Health 52 Organization has launched a worldwide clinical trial called SOLIDARITY to test 53 antiviral treatment options for the novel coronavirus, but as of April 15, 2020, there 54 are no specific drugs for treating COVID-19 1 . Many research teams worldwide are 55 racing to develop vaccines against SARS-CoV-2 to combat this novel coronavirus 56 pandemic. 57 Similar to other coronaviruses, SARS-CoV-2 is an enveloped positive-stranded RNA 58 virus with four major structural proteins: S (spike), E (envelope), M (membrane), and 59 N (nucleocapsid) proteins 2-4 . The surface S protein is the key that allows SARS-COV-60 2 to enter into cells 5 , as it plays a role in binding to the cellular receptor and 61 membrane fusion 5,6 . The SARS-CoV-2 shares 75.96% homology with the 2003 62 SARS-CoV 3 , and the structure and functional domains of the SARS-CoV-2 S protein 63 have already been identified 7 . The receptor-binding domain...

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Mapping the Immunodominance Landscape of SARS-CoV-2 Spike Protein for the Design of Vaccines against COVID-19

Zhang

Chen

et al. 2020

Preprint

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“…Fusion of the viral and host cell membranes is facilitated by the spike glycoprotein, which undergoes a significant conformational change within its structures [18,21,22]. SARS-CoV-2 studies suggest [18,23,24] that the spike glycoprotein functions as a homotrimer. The recognition and subsequently fusion of two membranes from the virus and the host is triggered by the S1 subunit, which binds the host cell receptor: angiotensin-converting enzyme 2 (ACE2) [16,[25][26][27][28][29][30][31].…”

Section: Introductionmentioning

confidence: 99%

Highly Conserved Homotrimer Cavity Formed by the SARS-CoV-2 Spike Glycoprotein: A Novel Binding Site

Kalathiya

Padariya

Mayordomo

et al. 2020

Preprint

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An important stage in SARS-CoV-2 life cycle is the fusion of spike(S) protein with the ACE2 host-cell receptor. Therefore, to explore conserved features in S protein dynamics and to identify potentially novel regions for drugging, we measured variability derived from 791 viral genomes and studied its properties by MD simulation. The findings indicated that S2 subunit (HR1, CH, and CD domains) showed low variability, low fluctuations in MD, and displayed a trimer cavity. By contrast, the RBD domain, which is typically targeted in drug discovery programmes, exhibits more sequence variability and flexibility. Interpretations from MD suggest that the monomer is in constant motion showing transitions up-to-down state, and the trimer cavity may function as a 'bouncing spring' that may facilitates S protein interactions with ACE2. Feasibility of trimer cavity for potential drug target was examined by SBVS screening. Several hits that have already been validated or suggested to inhibit the SARS-CoV-2 virus in cell systems were identified; in particular, the data suggest an action mechanism for such molecules including Chitosan and macrolide types. These findings identify a novel binding-site formed by the S protein, that might assist in future drug discovery programmes aimed at targeting the CoV family of viruses.

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“…The crucial role played by the spike protein is also due to the possibility to use the recombinant SARS-CoV-2 spike protein for triggering immune response, working as a vaccine, that may help in preventing and treating COVID- 19, similarly to what proposed recently (24)(25)(26).…”

Section: Introductionmentioning

confidence: 94%

“…understanding virus invasion mechanisms, developing new vaccines or antibodies, identifying small molecules with high affinity for viral proteins and establishing quick/safe diagnosis selective/specific kits. Indeed, the scientific community is now focused in the development of new weapons for containing SARS-CoV-2 spread and COVID-19 complications as it could be observed in the enormous effort in developing new vaccines based on a virus protein/nucleic acid portion able to induce an efficient and specific immunogenic response(56)(57)(58)(59)(60), or in developing a neutralizing antibody highly specific for SARS-CoV-2 spike RBD(25,26,(61)(62)(63)(64), or in identifying chemicals with high affinity for SARS-CoV-2 crucial proteins (1-3, 65-67).…”

mentioning

confidence: 99%

Protein structure analysis of the interactions between SARS-CoV-2 spike protein and the human ACE2 receptor: from conformational changes to novel neutralizing antibodies

Mercurio

Tragni

Busco

et al. 2020

Preprint

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Abbreviations: Severe acute respiratory syndrome, SARS; coronavirus CoV; receptor binding domain, RBD; angiotensin converting enzyme 2, ACE2; fragment antigen binding, FAB; Word Health Organizzation, WHO; complementary-determining regions, (CDR); SwissPDBViewer, SPDBV. ABSTRACT The recent severe acute respiratory syndrome, known as Corona Virus Disease 2019 (COVID-19) has spread so much rapidly and severely to induce World Health Organization (WHO) to declare state of emergency over the new coronavirus SARS-CoV-2 pandemic. While several countries have chosen the almost complete lock-down for slowing down SARS-CoV-2 spread, scientific community is called to respond to the devastating outbreak by identifying new tools for diagnosis and treatment of the dangerous COVID-19. With this aim we performed an in silico comparative modeling analysis, which allows to gain new insights about the main conformational changes occurring in the SARS-CoV-2 spike protein, at the level of the receptor binding domain (RBD), along interactions with human cells angiotensin converting enzyme 2 (ACE2) receptor, that favour human cell invasion. Furthermore, our analysis provides i) an ideal pipeline to identify already characterized antibodies that might target SARS-CoV-2 spike RBD, for preventing interactions with the human ACE2, and ii) instructions for building new possible neutralizing antibodies, according to chemical/physical space restraints and complementary determining regions (CDR) mutagenesis of the identified existing antibodies. The proposed antibodies show in silico a high affinity for SARS-CoV-2 spike RBD and can be used as reference antibodies also for building new high affinity antibodies against present and future coronavirus able to invade human cells through interactions of their spike proteins with the human ACE2. More in general, our analysis provides indications for the set-up of the right biological molecular context for investigating spike RBD-ACE2 interactions for the development of new vaccines, diagnosis kits and other treatments based on the usage or the targeting of SARS-CoV-2 spike protein.

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Spike protein binding prediction with neutralizing antibodies of SARS-CoV-2

Cited by 36 publications

References 48 publications

Mapping the Immunodominance Landscape of SARS-CoV-2 Spike Protein for the Design of Vaccines against COVID-19

Mapping the Immunodominance Landscape of SARS-CoV-2 Spike Protein for the Design of Vaccines against COVID-19

Highly Conserved Homotrimer Cavity Formed by the SARS-CoV-2 Spike Glycoprotein: A Novel Binding Site

Protein structure analysis of the interactions between SARS-CoV-2 spike protein and the human ACE2 receptor: from conformational changes to novel neutralizing antibodies

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