scholarly journals Monoclonal antibodies capable of binding SARS‐CoV‐2 spike protein receptor‐binding motif specifically prevent GM‐CSF induction

2021 ◽  
Author(s):  
Xiaoling Qiang ◽  
Shu Zhu ◽  
Jianhua Li ◽  
Weiqiang Chen ◽  
Huan Yang ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Receptor Binding ◽  
Spike Protein ◽  
Binding Motif ◽  
Gm Csf ◽  
Protein Receptor

scholarly journals Monoclonal Antibodies Capable of Binding SARS-CoV-2 Spike Protein Receptor Binding Motif Specifically Prevent GM-CSF Induction

2020 ◽  
Author(s):  
Xiaoling Qiang ◽  
Shu Zhu ◽  
Jianhua Li ◽  
Ping Wang ◽  
Kevin J. Tracey ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Receptor Binding ◽  
Viral Entry ◽  
Protein Targeting ◽  
Inflammatory Responses ◽  
Human Monocyte ◽  
Spike Protein ◽  
Binding Motif ◽  
Gm Csf ◽  
Future Assessment

AbstractA severe acute respiratory syndrome (SARS)-like coronavirus (SARS-CoV-2) has recently caused a pandemic COVID-19 disease that infected more than 25.6 million and killed 852,000 people worldwide. Like the SARS-CoV, SARS-CoV-2 also employs a receptor-binding motif (RBM) of its envelope spike protein for binding the host angiotensin-converting enzyme 2 (ACE2) to gain viral entry. Currently, extensive efforts are being made to produce vaccines against a surface fragment of a SARS-CoV-2, such as the spike protein, in order to boost protective antibody responses. It was previously unknown how spike protein-targeting antibodies would affect innate inflammatory responses to SARS-CoV-2 infections. Here we generated a highly purified recombinant protein corresponding to the RBM of SARS-CoV-2, and used it to screen for cross-reactive monoclonal antibodies (mAbs). We found two RBM-binding mAbs that competitively inhibited its interaction with human ACE2, and specifically blocked the RBM-induced GM-CSF secretion in both human monocyte and murine macrophage cultures. Our findings have suggested a possible strategy to prevent SARS-CoV-2-elicited “cytokine storm”, and provided a potentially useful criteria for future assessment of innate immune-modulating properties of various SARS-CoV-2 vaccines.One Sentence SummaryRBM-binding Antibodies Inhibit GM-CSF Induction.

Compared with SARS-CoV2 wild type's spike protein, the SARS-CoV2 omicron's receptor binding motif has adopted a more SARS-CoV1 and/or bat/civet-like structure.

2021 ◽  
Author(s):  
Michael O. Glocker ◽  
Kwabena F. M. Opuni ◽  
Hans-Juergen Thiesen
Keyword(s):  
Free Energy ◽  
Receptor Binding ◽  
Free Energy Calculations ◽  
Viral Fitness ◽  
Spike Protein ◽  
Receptor Protein ◽  
Binding Motif ◽  
Energy Calculations ◽  
Selection Processes ◽  
Protein Receptor

Our study focuses on free energy calculations of SARS-Cov2 spike protein receptor binding motives (RBMs) from wild type and variants-of-concern with particular emphasis on currently emerging SARS- CoV2 omicron variants of concern (VOC). Our computational free energy analysis underlines the occurrence of positive selection processes that specify omicron host adaption and bring changes on the molecular level into context with clinically relevant observations. Our free energy calculations studies regarding the interaction of omicron's RBM with human ACE2 shows weaker binding to ACE2 than alpha's, delta's, or wild type's RBM. Thus, less virus is predicted to be generated in time per infected cell. Our mutant analyses predict with focus on omicron variants a reduced spike-protein binding to ACE2--receptor protein possibly enhancing viral fitness / transmissibility and resulting in a delayed induction of danger signals as trade-off. Finally, more virus is produced but less per cell accompanied with delayed Covid-19 immunogenicity and pathogenicity. Regarding the latter, more virus is assumed to be required to initiate inflammatory immune responses.

scholarly journals Deamidation drives molecular aging of the SARS-CoV-2 spike protein receptor-binding motif

2021 ◽  
pp. 101175
Author(s):  
Ramiro Lorenzo ◽  
Lucas A. Defelipe ◽  
Lucio Aliperti ◽  
Stephan Niebling ◽  
Tânia F. Custódio ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Spike Protein ◽  
Binding Motif ◽  
Protein Receptor ◽  
Molecular Aging

scholarly journals V483A: an emerging mutation hotspot of SARS-CoV-2

2021 ◽  
Author(s):  
Omar Ashwaq ◽  
Pratibha Manickavasagam ◽  
SK Manirul Haque
Keyword(s):  
Monoclonal Antibodies ◽  
North America ◽  
Receptor Binding ◽  
Viral Genome ◽  
Spike Protein ◽  
Occurrence Rate ◽  
Binding Motif ◽  
Wild Type ◽  
The Many ◽  
Cell Interface

One of the many mutations that have occurred in the viral genome is the V483A mutation, which is a part of the receptor-binding motif present in the S1 domain of the spike protein. V483A mutant virus is popular in North America with 36 cases so far and frequently occurring in recent days. This review compares the wild-type and the V483A mutants to analyze certain factors like the interaction between the virus and host-cell interface, binding affinity, stability, partition energy, hydrophobicity, occurrence rate and transmissibility. This information can be of monumental importance in vaccine and drug development since the mutants can become resistant to the vaccines and monoclonal antibodies.

scholarly journals Design of a companion bioinformatic tool to detect the emergence and geographical distribution of SARS-CoV-2 Spike protein genetic variants

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Alice Massacci ◽  
Eleonora Sperandio ◽  
Lorenzo D’Ambrosio ◽  
Mariano Maffei ◽  
Fabio Palombo ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Consensus Sequence ◽  
Cell Epitope ◽  
Vaccine Design ◽  
Binding Domain ◽  
Spike Protein ◽  
Antibody Activity ◽  
Binding Motif ◽  
Receptor Binding Domain ◽  
The Impact

Abstract Background Tracking the genetic variability of Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) is a crucial challenge. Mainly to identify target sequences in order to generate robust vaccines and neutralizing monoclonal antibodies, but also to track viral genetic temporal and geographic evolution and to mine for variants associated with reduced or increased disease severity. Several online tools and bioinformatic phylogenetic analyses have been released, but the main interest lies in the Spike protein, which is the pivotal element of current vaccine design, and in the Receptor Binding Domain, that accounts for most of the neutralizing the antibody activity. Methods Here, we present an open-source bioinformatic protocol, and a web portal focused on SARS-CoV-2 single mutations and minimal consensus sequence building as a companion vaccine design tool. Furthermore, we provide immunogenomic analyses to understand the impact of the most frequent RBD variations. Results Results on the whole GISAID sequence dataset at the time of the writing (October 2020) reveals an emerging mutation, S477N, located on the central part of the Spike protein Receptor Binding Domain, the Receptor Binding Motif. Immunogenomic analyses revealed some variation in mutated epitope MHC compatibility, T-cell recognition, and B-cell epitope probability for most frequent human HLAs. Conclusions This work provides a framework able to track down SARS-CoV-2 genomic variability.

scholarly journals SARS-CoV-2 convergent evolution as a guide to explore adaptive advantage

2021 ◽  
Author(s):  
Jiri Zahradnik ◽  
Jaroslav Nunvar ◽  
Gideon Schreiber
Keyword(s):  
Receptor Binding ◽  
Convergent Evolution ◽  
Great Majority ◽  
Viral Population ◽  
Binding Motif ◽  
Furin Cleavage ◽  
S Protein ◽  
Adaptive Mutations ◽  
Furin Cleavage Site ◽  
Protein Receptor

Much can be learned from 1.2 million sequences of SARS-CoV-2 generated during the last 15 months. Out of the overwhelming number of mutations sampled so far, only few rose to prominence in the viral population. Many of these emerged recently and independently in multiple lineages. Such a textbook example of convergent evolution at the molecular level is not only curiosity but a guide to uncover the basis for adaptive advantage behind these events. Focusing on the extent of the convergent evolution in the spike (S) protein, our report confirms that the most concerning SARS-CoV-2 lineages carry the heaviest burden of convergent S-protein mutations, suggesting their fundamental adaptive advantage. The great majority (21/25) of S-protein sites under convergent evolution tightly cluster in three functional domains; N-terminal domain, receptor-binding domain, and Furin cleavage site. We further show that among the S-protein receptor-binding motif mutations, ACE2 affinity-improving substitutions are favored. While the probed mutation space in the S protein covered all amino-acids reachable by single nucleotide changes, substitutions requiring two nucleotide changes or epistatic mutations of multiple-residues have only recently started to emerge. Unfortunately, despite their convergent emergence and physical association, most of these adaptive mutations and their combinations remain understudied. We aim to promote research of current variants which are currently understudied but may become important in the future.

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