scholarly journals The molecular basis for SARS-CoV-2 binding to dog ACE2

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Zengyuan Zhang ◽  
Yanfang Zhang ◽  
Kefang Liu ◽  
Yan Li ◽  
Qiong Lu ◽  
...  
Keyword(s):  
Binding Affinity ◽  
Molecular Basis ◽  
Domestic Animals ◽  
Receptor Binding Domain ◽  
Salt Bridges ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Binding Interface ◽  
Protein Receptor ◽  
Contact Residues

AbstractSARS-CoV-2 can infect many domestic animals, including dogs. Herein, we show that dog angiotensin-converting enzyme 2 (dACE2) can bind to the SARS-CoV-2 spike (S) protein receptor binding domain (RBD), and that both pseudotyped and authentic SARS-CoV-2 can infect dACE2-expressing cells. We solved the crystal structure of RBD in complex with dACE2 and found that the total number of contact residues, contact atoms, hydrogen bonds and salt bridges at the binding interface in this complex are slightly fewer than those in the complex of the RBD and human ACE2 (hACE2). This result is consistent with the fact that the binding affinity of RBD to dACE2 is lower than that of hACE2. We further show that a few important mutations in the RBD binding interface play a pivotal role in the binding affinity of RBD to both dACE2 and hACE2. Our work reveals a molecular basis for cross-species transmission and potential animal spread of SARS-CoV-2, and provides new clues to block the potential transmission chains of this virus.

scholarly journals The molecular basis for SARS-CoV-2 recognized by dog ACE2

2021 ◽  
Author(s):  
Zengyuan Zhang ◽  
Yanfang Zhang ◽  
Kefang Liu ◽  
Yan Li ◽  
Qiong Lu ◽  
...  
Keyword(s):  
Binding Affinity ◽  
Molecular Basis ◽  
Domestic Animals ◽  
Salt Bridges ◽  
Binding Region ◽  
Angiotensin Converting Enzyme 2 ◽  
Binding Interface ◽  
Protein Receptor ◽  
Contact Residues ◽  
Receptor Binding Region

Abstract SARS-CoV-2 can infect many domestic animals, including dogs. Herein, we show that dog angiotensin converting enzyme 2 (dACE2) can bind to SARS-CoV-2 spike (S) protein receptor binding region (RBD), and that both pseudotyped and authentic SARS-CoV-2 can infect dACE2-expressing cells. we solved the crystal structure of RBD in complex with dACE2 and found that the total numbers of contact residues, contact atoms, hydrogen bonds and salt bridges at the binding interface in this complex are slightly fewer than those in the complex of the RBD and human ACE2 (hACE2). This result is consistent with the fact that the binding affinity of RBD to dACE2 is lower than that to hACE2. We further show that a few important mutations in the RBD binding interface play a pivotal role in the binding affinity of RBD to both dACE2 and hACE2, and need intense monitoring and controlling.

Identification of the interaction between Angiotensin-converting Enzyme Residues and Severe Acute Respiratory Syndrome Coronavirus 2.

2021 ◽  
Vol 27 ◽  
Author(s):  
Youness Kadil ◽  
Mohammed Mouhcine ◽  
Imane Rahmoune ◽  
Houda Filali
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Angiotensin Converting Enzyme ◽  
Receptor Binding Domain ◽  
Converting Enzyme ◽  
Methodological Study ◽  
Angiotensin Converting Enzyme 2 ◽  
Enveloped Virus ◽  
Positive Sense ◽  
Contact Residues ◽  
Cell Membrane Protein

Introduction: Coronaviruses are an enveloped virus with a positive-sense single-stranded RNA genome. It has been shown that the viral spike S glycoprotein binds to the cell membrane protein angiotensin-converting enzyme 2 as an invasive process of the virus. The aim of this research is the application of a computational approach in the identification of the interaction residues ACE2 with severe acute respiratory syndrome Coronavirus 2. A methodological study to understand the interactions between SARS CoV2 and ACE2, which is essential for the development of a vaccine and an antiviral. Methods: The S protein is cleaved into two subunits, S1 and S2. S1 contains the receptor-binding domain (RBD) which allows the virus to bind directly to the peptidase domain of ACE2. Results: Our results present the overall differences in contact residues between the different chains, and an alignment between the two SARS Viruses, along with a presentation of similarity between them.Then S2 likely plays a role in membrane fusion. Conclusions : The synthesis of our results appears to provide potentially a rational set of objectives that can help in the development of a SARS-CoV-2 vaccine.

scholarly journals Possible Transmission Flow of SARS-CoV-2 Based on ACE2 Features

Molecules ◽  
2020 ◽  
Vol 25 (24) ◽  
pp. 5906
Author(s):  
Sk. Sarif Hassan ◽  
Shinjini Ghosh ◽  
Diksha Attrish ◽  
Pabitra Pal Choudhury ◽  
Alaa A. A. Aljabali ◽  
...  
Keyword(s):  
Amino Acids ◽  
Severe Acute Respiratory Syndrome ◽  
Angiotensin Converting Enzyme ◽  
Receptor Binding ◽  
Comprehensive Analysis ◽  
Cellular Receptor ◽  
Receptor Binding Domain ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Protein Receptor

Angiotensin-converting enzyme 2 (ACE2) is the cellular receptor for the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) that is engendering the severe coronavirus disease 2019 (COVID-19) pandemic. The spike (S) protein receptor-binding domain (RBD) of SARS-CoV-2 binds to the three sub-domains viz. amino acids (aa) 22–42, aa 79–84, and aa 330–393 of ACE2 on human cells to initiate entry. It was reported earlier that the receptor utilization capacity of ACE2 proteins from different species, such as cats, chimpanzees, dogs, and cattle, are different. A comprehensive analysis of ACE2 receptors of nineteen species was carried out in this study, and the findings propose a possible SARS-CoV-2 transmission flow across these nineteen species.

scholarly journals Covalent Bonding Aptamer with Enhanced SARS-CoV-2 RBD-ACE2 Blocking and Pseudovirus Neutralization Activities

2021 ◽  
Author(s):  
Zichen Qin ◽  
Yiying Zhu ◽  
Yu Xiang
Keyword(s):  
Covalent Bonding ◽  
Host Cells ◽  
Receptor Binding Domain ◽  
Covalent Bonds ◽  
Angiotensin Converting Enzyme 2 ◽  
Drug Candidates ◽  
Chemically Modified ◽  
Binding Interface ◽  
Covalent Inhibition ◽  
Protein Receptor

SARS-CoV-2 uses its spike protein receptor-binding domain (RBD) to interact with the angiotensin-converting enzyme 2 (ACE2) receptor on host cells. Inhibitors of the RBD-ACE2 interaction are therefore promising drug candidates in treating COVID-19. Here, we report a covalent bonding aptamer that can block the RBD-ACE2 interaction and neutralize SARS-CoV-2 pseudovirus infection by forming covalent bonds on RBD, resulting in more than 25-fold enhancement of pseudovirus neutralization efficacy over the original binding aptamer. The chemically modified aptamer is equipped with sulfur(VI) fluoride exchange (SuFEx) modifications and covalently targets important RBD residues within the RBD-ACE2 binding interface, including Y453 and R408. The covalent bonding is highly specific to RBD over other proteins such as human serum albumin (HSA), ACE2 and immunoglobulin G1 (IgG1) Fc. Our study demonstrates the promise of introducing covalent inhibition mechanisms for developing robust RBD-ACE2 inhibitors against SARS-CoV-2 infection.

scholarly journals S19W, T27W, and N330Y mutations in ACE2 enhance SARS-CoV-2 S-RBD binding toward both wild-type and antibody-resistant viruses and its molecular basis

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Fei Ye ◽  
Xi Lin ◽  
Zimin Chen ◽  
Fanli Yang ◽  
Sheng Lin ◽  
...  
Keyword(s):  
Molecular Basis ◽  
Structural Data ◽  
Van Der Waals Interactions ◽  
Side Chains ◽  
Receptor Binding Domain ◽  
Converting Enzyme ◽  
Wild Type ◽  
Angiotensin Converting Enzyme 2 ◽  
Domain Protein ◽  
Entry Inhibition

AbstractSARS-CoV-2 recognizes, via its spike receptor-binding domain (S-RBD), human angiotensin-converting enzyme 2 (ACE2) to initiate infection. Ecto-domain protein of ACE2 can therefore function as a decoy. Here we show that mutations of S19W, T27W, and N330Y in ACE2 could individually enhance SARS-CoV-2 S-RBD binding. Y330 could be synergistically combined with either W19 or W27, whereas W19 and W27 are mutually unbeneficial. The structures of SARS-CoV-2 S-RBD bound to the ACE2 mutants reveal that the enhanced binding is mainly contributed by the van der Waals interactions mediated by the aromatic side-chains from W19, W27, and Y330. While Y330 and W19/W27 are distantly located and devoid of any steric interference, W19 and W27 are shown to orient their side-chains toward each other and to cause steric conflicts, explaining their incompatibility. Finally, using pseudotyped SARS-CoV-2 viruses, we demonstrate that these residue substitutions are associated with dramatically improved entry-inhibition efficacy toward both wild-type and antibody-resistant viruses. Taken together, our biochemical and structural data have delineated the basis for the elevated S-RBD binding associated with S19W, T27W, and N330Y mutations in ACE2, paving the way for potential application of these mutants in clinical treatment of COVID-19.

scholarly journals Withanone from Withania somnifera May Inhibit Novel Coronavirus (COVID-19) Entry by Disrupting Interactions between Viral S-Protein Receptor Binding Domain and Host ACE2 Receptor

2020 ◽  
Author(s):  
Acharya Balkrishna ◽  
SUBARNA POKHREL ◽  
Jagdeep Singh ◽  
Anurag Varshney
Keyword(s):  
Receptor Binding ◽  
Withania Somnifera ◽  
Binding Domain ◽  
Host Cells ◽  
Receptor Binding Domain ◽  
Salt Bridges ◽  
Binding Interface ◽  
Electrostatic Component ◽  
Protein Receptor ◽  
First Choice

Abstract Background Newly emerged COVID-19 has been shown to engage the host cell ACE2 through its spike protein receptor binding domain (RBD). Here we show that natural phytochemical from a medicinal herb, Withania somnifera, have distinct effects on viral RBD and host ACE2 receptor complex. Methods We employed molecular docking to screen thousands of phytochemicals against the ACE2-RBD complex, performed molecular dynamics (MD) simulation, and estimated the electrostatic component of binding free energy, along with the computation of salt bridge electrostatics. Results We report that W. somnifera compound, Withanone, docked very well in the binding interface of AEC2-RBD complex, and was found to move slightly towards the interface centre on simulation. Withanone significantly decreased electrostatic component of binding free energies of ACE2-RBD complex. Two salt bridges were also identified at the interface; incorporation of Withanone destabilized these salt bridges and decreased their occupancies. We postulate, such an interruption of electrostatic interactions between the RBD and ACE2 would block or weaken COVID-19 entry and its subsequent infectivity. Conclusion Our data, for the first time, show that natural phytochemicals could well be the viable options for controlling COVID-19 entry into host cells, and W. somnifera may be the first choice of herbs in these directions to curb the COVID-19 infectivity.

Effective ACE2 Peptide-Nanoparticle Conjugation and Its Binding with SARS-Cov-2 RBD Quantified by Dynamic Light Scattering

2021 ◽  
Author(s):  
Vince St. Dollente Mesias ◽  
Hongni Zhu ◽  
Xiao Tang ◽  
Xin Dai ◽  
Yusong Guo ◽  
...  
Keyword(s):  
Light Scattering ◽  
Dynamic Light Scattering ◽  
Angiotensin Converting Enzyme ◽  
Receptor Binding ◽  
Spike Protein ◽  
Cellular Receptor ◽  
Receptor Binding Domain ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Protein Receptor

The infection of coronavirus initiates with the binding between its spike protein receptor binding domain (RBD) and a human cellular receptor called angiotensin-converting enzyme 2 (ACE2). Here, we construct truncated...

scholarly journals Competitive SARS-CoV-2 Serology Reveals Most Antibodies Targeting the Spike Receptor-Binding Domain Compete for ACE2 Binding

mSphere ◽  
2020 ◽  
Vol 5 (5) ◽  
Author(s):  
James R. Byrnes ◽  
Xin X. Zhou ◽  
Irene Lui ◽  
Susanna K. Elledge ◽  
Jeff E. Glasgow ◽  
...  
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Receptor Binding ◽  
Viral Entry ◽  
Binding Domain ◽  
Spike Protein ◽  
Receptor Binding Domain ◽  
Converting Enzyme ◽  
Block Interaction ◽  
Angiotensin Converting Enzyme 2 ◽  
Protein Receptor

ABSTRACT As severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to spread around the world, there is an urgent need for new assay formats to characterize the humoral response to infection. Here, we present an efficient, competitive serological assay that can simultaneously determine an individual’s seroreactivity against the SARS-CoV-2 Spike protein and determine the proportion of anti-Spike antibodies that block interaction with the human angiotensin-converting enzyme 2 (ACE2) required for viral entry. In this approach based on the use of enzyme-linked immunosorbent assays (ELISA), we present natively folded viral Spike protein receptor-binding domain (RBD)-containing antigens via avidin-biotin interactions. Sera are then competed with soluble ACE2-Fc, or with a higher-affinity variant thereof, to determine the proportion of ACE2 blocking anti-RBD antibodies. Assessment of sera from 144 SARS-CoV-2 patients ultimately revealed that a remarkably consistent and high proportion of antibodies in the anti-RBD pool targeted the epitope responsible for ACE2 engagement (83% ± 11%; 50% to 107% signal inhibition in our largest cohort), further underscoring the importance of tailoring vaccines to promote the development of such antibodies. IMPORTANCE With the emergence and continued spread of the SARS-CoV-2 virus, and of the associated disease, coronavirus disease 2019 (COVID-19), there is an urgent need for improved understanding of how the body mounts an immune response to the virus. Here, we developed a competitive SARS-CoV-2 serological assay that can simultaneously determine whether an individual has developed antibodies against the SARS-CoV-2 Spike protein receptor-binding domain (RBD) and measure the proportion of these antibodies that block interaction with the human angiotensin-converting enzyme 2 (ACE2) required for viral entry. Using this assay and 144 SARS-CoV-2 patient serum samples, we found that a majority of anti-RBD antibodies compete for ACE2 binding. These results not only highlight the need to design vaccines to generate such blocking antibodies but also demonstrate the utility of this assay to rapidly screen patient sera for potentially neutralizing antibodies.

scholarly journals Possible transmission flow of SARS-CoV-2 based on ACE2 features

2020 ◽  
Author(s):  
Sk. Sarif Hassan ◽  
Shinjini Ghosh ◽  
Diksha Attrish ◽  
Pabitra Pal Choudhury ◽  
Vladimir N. Uversky ◽  
...  
Keyword(s):  
Amino Acids ◽  
Severe Acute Respiratory Syndrome ◽  
Angiotensin Converting Enzyme ◽  
Receptor Binding ◽  
Comprehensive Analysis ◽  
Cellular Receptor ◽  
Receptor Binding Domain ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Protein Receptor

AbstractAngiotensin-converting enzyme 2 (ACE2) is the cellular receptor for the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) that is engendering the severe coronavirus disease 2019 (COVID-19) pandemic. The spike (S) protein receptor-binding domain (RBD) of SARS-CoV-2 binds to the three sub-domains viz. amino acids (aa) 22-42, aa 79-84, and aa 330-393 of ACE2 on human cells to initiate entry. It was reported earlier that the receptor utilization capacity of ACE2 proteins from different species, such as cats, chimpanzees, dogs, and cattle, are different. A comprehensive analysis of ACE2 receptors of nineteen species was carried out in this study, and the findings propose a possible SARS-CoV-2 transmission flow across these nineteen species.

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