scholarly journals Comparative Genomics of Receptor Binding Domains of Spike Protein and Receptor Interaction in COVID-19 Patient

2020 ◽  
Author(s):  
Rimjhim Dasgupta
Keyword(s):  
Receptor Binding ◽  
Binding Domain ◽  
Host Cells ◽  
Receptor Interaction ◽  
Receptor Binding Domain ◽  
Furin Cleavage ◽  
S Protein ◽  
Human Coronaviruses ◽  
Novel Coronavirus ◽  
Bat Coronavirus

The current outbreak of viral pneumonia in the city of Wuhan, China, was caused by a novel coronavirus designated 2019-nCoV, as determined by sequencing the viral RNA genome. Among its genome, S protein is surface-exposed and mediates entry into host cells. Currently it is one of the main targets for designing antibodies (Abs), therapeutic and vaccine. Earlier studies stated that ACE2 (angiotensin converting enzyme 2) could facilitate S protein mediated entry for this newly emerged coronavirus. Here we have taken an attempt to compare the genetic structure of receptor binding domain within S protein of highly pathogenic human coronaviruses (special reference to 2019-nCoV) with Bat coronavirus RaTG13. We have compared 2019-nCov receptor binding domain (RBD) with other pathogenic human coronaviruses (MERS-CoV and SARS-CoV) and Bat coronavirus RaTG13. We found that it is closest to RaTG13 RBD than MERS-CoV and SARS-CoV. Our study shows that 2019-nCov RBD also has significant identity with pangolin S protein RBD. We have also predicted the amino acid residues within RDB those may play important role for ACE2 receptor interaction. We identified unique signature for furin cleavage in 2019-nCov S protein but not in of other pathogenic human coronaviruses (tested here), bat coronavirus RaTG13 or pangolin.

scholarly journals Cross-reactive neutralization of SARS-CoV-2 by serum antibodies from recovered SARS patients and immunized animals

2020 ◽  
Vol 6 (45) ◽  
pp. eabc9999 ◽  
Author(s):  
Yuanmei Zhu ◽  
Danwei Yu ◽  
Yang Han ◽  
Hongxia Yan ◽  
Huihui Chong ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Receptor Binding ◽  
Binding Domain ◽  
Full Length ◽  
Receptor Binding Domain ◽  
Serum Antibodies ◽  
Serum Samples ◽  
S Protein ◽  
Novel Coronavirus

The current coronavirus disease 2019 (COVID-19) pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus genetically close to SARS-CoV. To investigate the effects of previous SARS-CoV infection on the ability to recognize and neutralize SARS-CoV-2, we analyzed 20 convalescent serum samples collected from individuals infected with SARS-CoV during the 2003 SARS outbreak. All patient sera reacted strongly with the S1 subunit and receptor binding domain (RBD) of SARS-CoV; cross-reacted with the S ectodomain, S1, RBD, and S2 proteins of SARS-CoV-2; and neutralized both SARS-CoV and SARS-CoV-2 S protein–driven infections. Analysis of antisera from mice and rabbits immunized with a full-length S and RBD immunogens of SARS-CoV verified cross-reactive neutralization against SARS-CoV-2. A SARS-CoV–derived RBD from palm civets elicited more potent cross-neutralizing responses in immunized animals than the RBD from a human SARS-CoV strain, informing strategies for development of universal vaccines against emerging coronaviruses.

scholarly journals Xeno-Nucleic Acid (XNA) 2’-Fluoro-Arabino Nucleic Acid (FANA) Aptamers to the Receptor-Binding Domain of SARS-CoV-2 S Protein Block ACE2 Binding

Viruses ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 1983
Author(s):  
Irani Alves Ferreira-Bravo ◽  
Jeffrey J. DeStefano
Keyword(s):  
Nucleic Acid ◽  
Receptor Binding ◽  
Neutralizing Antibodies ◽  
Dissociation Constants ◽  
High Specificity ◽  
Binding Domain ◽  
Host Cells ◽  
Receptor Binding Domain ◽  
S Protein ◽  
Equilibrium Dissociation Constants

The causative agent of COVID-19, SARS-CoV-2, gains access to cells through interactions of the receptor-binding domain (RBD) on the viral S protein with angiotensin-converting enzyme 2 (ACE2) on the surface of human host cells. Systematic evolution of ligands by exponential enrichment (SELEX) was used to generate aptamers (nucleic acids selected for high binding affinity to a target) to the RBD made from 2ʹ-fluoro-arabinonucleic acid (FANA). The best selected ~79 nucleotide aptamers bound the RBD (Arg319-Phe541) and the larger S1 domain (Val16-Arg685) of the 1272 amino acid S protein with equilibrium dissociation constants (KD,app) of ~10–20 nM, and binding half-life for the RBD, S1 domain, and full trimeric S protein of 53 ± 18, 76 ± 5, and 127 ± 7 min, respectively. Aptamers inhibited the binding of the RBD to ACE2 in an ELISA assay. Inhibition, on a per weight basis, was similar to neutralizing antibodies that were specific for RBD. Aptamers demonstrated high specificity, binding with about 10-fold lower affinity to the related S1 domain from the original SARS virus, which also binds to ACE2. Overall, FANA aptamers show affinities comparable to previous DNA aptamers to RBD and S1 protein and directly block receptor interactions while using an alternative Xeno-nucleic acid (XNA) platform.

scholarly journals Predicting the Efficacy of COVID-19 Convalescent Plasma Donor Units with the Lumit Dx anti-Receptor Binding Domain Assay

2021 ◽  
Author(s):  
Sanath Kumar Janaka ◽  
Natasha M Clark ◽  
David T Evans ◽  
Joseph P Connor
Keyword(s):  
Receptor Binding ◽  
Therapeutic Option ◽  
Passive Immunization ◽  
Binding Domain ◽  
Receptor Binding Domain ◽  
S Protein ◽  
Antibody Assays ◽  
Antibody Titers ◽  
Novel Coronavirus ◽  
Design And Methods

AbstractBackgroundThe novel coronavirus SARS-CoV2 that causes COVID-19 has resulted in the death of more than 2.5 million people, but no cure exists. Although passive immunization with COVID-19 convalescent plasma (CCP) provides a safe and viable therapeutic option, the selection of optimal units for therapy in a timely fashion remains a barrier.Study design and methodsSince virus neutralization is a necessary characteristic of plasma that can benefit recipients, the neutralizing titers of plasma samples were measured using a retroviral-pseudotype assay. Binding antibody titers to the spike (S) protein were also determined by a clinically available serological assay (Ortho-Vitros total IG), and an in-house ELISA. The results of these assays were compared to a measurement of antibodies directed to the receptor binding domain (RBD) of the SARS-CoV2 S protein (Promega Lumit Dx).ResultsAll measures of antibodies were highly variable, but correlated, to different degrees, with each other. However, the anti-RBD antibodies correlated with viral neutralizing titers to a greater extent than the other antibody assays.DiscussionOur observations support the use of an anti-RBD assay such as the Lumit Dx assay, as an optimal predictor of the neutralization capability of CCP.

scholarly journals Virtual Screening of Anti-Viral Drugs and Natural Compounds for Potential Inhibition of the Novel SARS-Cov-2 Spike Receptor-Binding Domain

2020 ◽  
Author(s):  
Shilu M. Mathew ◽  
Fatiha Benslimane ◽  
Asmaa A. Althani ◽  
Hadi M. Yassine
Keyword(s):  
Receptor Binding ◽  
Protein Structures ◽  
Natural Compounds ◽  
Binding Domain ◽  
Host Cells ◽  
Receptor Binding Domain ◽  
Binding Modes ◽  
S Protein ◽  
Computational Screening ◽  
Natural Drugs

Background: The spike (S) protein of SARS-CoV-2 harbors the receptor-binding domain (RBD) that mediates the virus's entry to host cells. The aim of this study was to identify novel inhibitors that target the RBD domain of S-protein through computational screening of chemical and natural compounds. Method: The S protein was modelled from the recently resolved and the previously described SARS-CoV protein structures. CLC Drug Discovery was used to computationally screen for potential inhibitory effects of currently prescribed drugs (n= 22) anti-viral natural drugs (n=100), natural compounds (n= 35032). QSAR was also performed. Results: Among currently precribed drugs to treat SARS-CoV2, hydroxychloroquine and favipiravir were identified as the best binders with an average of 4Hbonds, the binding affinity (BA): -36.66 kcal·mol−1, and interaction energy (IE): -6.63 kcal·mol−1. After the evaluation of anti-viral compounds, fosamprenavir and abacavir showed effective binding of 5H-bonds, with average BA: -18.75 kcal·mol−1, and IE: -3.57 kcal·mol−1. Furthermore, screening of 100 natural anti-viral compounds predicted potential binding modes of glycyrrhizin, nepritin, punicalagin, EGCG, and theaflavin (average BA: -49.88 kcal·mol−1, and IE: -4.35 kcal·mol−1). Additionally, the study reports 25 natural compounds that showed effective binding with an improved average BA: 51.46 kcal·mol−1. Conclusion: Using computational screening, we identified potential SARSCoV-2 spike inhibitors that bind to the RBD region.

scholarly journals The Receptor Binding Domain of SARS-CoV-2 Spike protein is the result of an ancestral recombination between the bat-CoV RaTG13 and the pangolin-CoV MP789

2020 ◽  
Author(s):  
Alejandro Flores-Alanis ◽  
Luisa Sandner-Miranda ◽  
Gabriela Delgado ◽  
Alejandro Cravioto ◽  
Rosario Morales-Espinosa
Keyword(s):  
Receptor Binding ◽  
Evolutionary History ◽  
Haplotype Network ◽  
Basic Function ◽  
Binding Domain ◽  
Receptor Binding Domain ◽  
S Protein ◽  
Parental Relationship ◽  
History Of ◽  
Novel Coronavirus

Abstract Objective: In December 2019 a novel coronavirus (SARS-CoV-2) that is causing the current COVID-19 pandemic was identified in Wuhan, China. Many questions have been raised about its origin and adaptation to humans. In the present work we performed a genetic analysis of the Spike glycoprotein (S) of SARS-CoV-2 and other related coronaviruses (CoVs) isolated from different hosts in order to trace the evolutionary history of this protein and the adaptation of SARS-CoV-2 to humans.Results: Based on the sequence analysis of the S gene, we suggest that the origin of SARS-CoV-2 is the result of recombination events between bat and pangolin CoVs. The hybrid SARS-CoV-2 ancestor jumped to humans and has been maintained by natural selection. Although the S protein of RaTG13 bat CoV has a high nucleotide identity with the S protein of SARS-CoV-2, the phylogenetic tree and the haplotype network suggest a non-direct parental relationship between these CoVs. Moreover, it is likely that the basic function of the receptor-binding domain (RBD) of S protein was acquired by the SARS-CoV-2 from the MP789 pangolin CoV by recombination and it has been highly conserved.

scholarly journals Interactions of the Receptor Binding Domain of SARS-CoV-2 Variants with hACE2: Insights from Molecular Docking Analysis and Molecular Dynamic Simulation

Biology ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 880
Author(s):  
Ismail Celik ◽  
Rohitash Yadav ◽  
Zekeriya Duzgun ◽  
Sarah Albogami ◽  
Ahmed M. El-Shehawi ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Experimental Studies ◽  
Point Mutations ◽  
Protein Docking ◽  
Binding Domain ◽  
Host Cells ◽  
Dynamics Simulation ◽  
Receptor Binding Domain ◽  
S Protein ◽  
The Impact

Since the beginning of the coronavirus 19 (COVID-19) pandemic in late 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been evolving through the acquisition of genomic mutations, leading to the emergence of multiple variants of concern (VOCs) and variants of interest (VOIs). Currently, four VOCs (Alpha, Beta, Delta, and Gamma) and seven VOIs (Epsilon, Zeta, Eta, Theta, Iota, Kappa, and Lambda) of SARS-CoV-2 have been identified in worldwide circulation. Here, we investigated the interactions of the receptor-binding domain (RBD) of five SARS-CoV-2 variants with the human angiotensin-converting enzyme 2 (hACE2) receptor in host cells, to determine the extent of molecular divergence and the impact of mutation, using protein-protein docking and dynamics simulation approaches. Along with the wild-type (WT) SARS-CoV-2, this study included the Brazilian (BR/lineage P.1/Gamma), Indian (IN/lineage B.1.617/Delta), South African (SA/lineage B.1.351/Beta), United Kingdom (UK/lineage B.1.1.7/Alpha), and United States (US/lineage B.1.429/Epsilon) variants. The protein-protein docking and dynamics simulation studies revealed that these point mutations considerably affected the structural behavior of the spike (S) protein compared to the WT, which also affected the binding of RBD with hACE2 at the respective sites. Additional experimental studies are required to determine whether these effects have an influence on drug–S protein binding and its potential therapeutic effect.

scholarly journals Xeno-nucleic Acid (XNA) 2'-Fluoro-Arabino Nucleic Acid (FANA) Aptamers to the Receptor Binding Domain of SARS-CoV-2 S Protein Block ACE2 Binding

2021 ◽  
Author(s):  
Irani Alves Ferreira-Bravo ◽  
Jeffrey J. DeStefano
Keyword(s):  
Nucleic Acid ◽  
Receptor Binding ◽  
Neutralizing Antibodies ◽  
Dissociation Constants ◽  
High Specificity ◽  
Binding Domain ◽  
Host Cells ◽  
Receptor Binding Domain ◽  
S Protein ◽  
Equilibrium Dissociation Constants

The causative agent of COVID-19, SARS-CoV-2, gains access to cells through interactions of the receptor binding domain (RBD) on the viral S protein with angiotensin converting enzyme 2 (ACE2) on the surface of human host cells. Systematic Evolution of Ligands by Exponential Enrichment (SELEX) was used to generate aptamers (nucleic acids selected for high binding affinity to a target) to the RBD made from 2′-fluoroarabinonucleic acid (FANA). The best selected ~ 79 nucleotide aptamers bound the RBD (Arg319-Phe541) and the larger S1 domain (Val16-Arg685) of the 1272 amino acid S protein with equilibrium dissociation constants (KD,app) of ~ 10-20 nM and a binding half-life for the RBD of 53 ± 18 minutes. Aptamers inhibited the binding of the RBD to ACE2 in an ELISA assay. Inhibition, on a per weight basis, was similar to neutralizing antibodies that were specific for RBD. Aptamers demonstrated high specificity, binding with about 10-fold lower affinity to the related S1 domain from the original SARS virus, which also binds to ACE2. Overall, FANA aptamers show affinities comparable to previous DNA aptamers to RBD and S protein and directly block receptor interactions while using an alternative Xeno-nucleic acid (XNA) platform.

scholarly journals Predicting the efficacy of COVID-19 convalescent plasma donor units with the Lumit Dx anti-receptor binding domain assay

PLoS ONE ◽  
2021 ◽  
Vol 16 (7) ◽  
pp. e0253551
Author(s):  
Sanath Kumar Janaka ◽  
Natasha M. Clark ◽  
David T. Evans ◽  
Huihui Mou ◽  
Michael Farzan ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Therapeutic Option ◽  
Passive Immunization ◽  
Binding Domain ◽  
Receptor Binding Domain ◽  
S Protein ◽  
Antibody Assays ◽  
Antibody Titers ◽  
Novel Coronavirus ◽  
Design And Methods

Background The novel coronavirus SARS-CoV2 that causes COVID-19 has resulted in the death of more than 2.5 million people, but no cure exists. Although passive immunization with COVID-19 convalescent plasma (CCP) provides a safe and viable therapeutic option, the selection of optimal units for therapy in a timely fashion remains a barrier. Study design and methods Since virus neutralization is a necessary characteristic of plasma that can benefit recipients, the neutralizing titers of plasma samples were measured using a retroviral-pseudotype assay. Binding antibody titers to the spike (S) protein were also determined by a clinically available serological assay (Ortho-Vitros total IG), and an in-house ELISA. The results of these assays were compared to a measurement of antibodies directed to the receptor binding domain (RBD) of the SARS-CoV2 S protein (Promega Lumit Dx). Results All measures of antibodies were highly variable, but correlated, to different degrees, with each other. However, the anti-RBD antibodies correlated with viral neutralizing titers to a greater extent than the other antibody assays. Discussion Our observations support the use of an anti-RBD assay such as the Lumit Dx assay, as an optimal predictor of the neutralization capability of CCP.

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