scholarly journals Analysis of COVID-19 Spike protein mutations and their effects on its affinity towards human cell receptors

2021 ◽  
Author(s):  
Abir Elbeji
Keyword(s):  
Comparative Analysis ◽  
Spike Protein ◽  
Host Recognition ◽  
The Novel ◽  
Positive Polarity ◽  
Angiotensin Converting Enzyme 2 ◽  
The Family ◽  
Novel Virus ◽  
Different Strains ◽  
Novel Coronavirus

Abstract The novel Coronavirus SARS-CoV-2 (2019-nCoV) is a member of the family Coronaviridae and contains a single-stranded RNA genome with positive-polarity. In order to reveal the evolution mechanism of the SARS-CoV2 genome, in particular its spike protein; the main driving force for host recognition, we conducted a comparative analysis with Coronaviruses of different strains, including MERS-CoV, SARS-CoV1 and Pangolin Coronavirus. In addition, a comparative analysis between the newly sequenced SARS-CoV2 from different regions of the world has been carried out in order to understand the evolution of this novel virus throughout its transmission. Among all sequenced strains, the latest France HCoV was the least identical to the reference. Further investigations have therefore been performed and it has been concluded that this strain has undergone mutations which have increased its binding affinity to the Angiotensin-Converting Enzyme 2 (ACE2) receptor, thus hypothetically increasing its infectivity.

scholarly journals Blocking Effect of Demethylzeylasteral on the Interaction between Human ACE2 Protein and SARS-CoV-2 RBD Protein Discovered Using SPR Technology

Molecules ◽  
2020 ◽  
Vol 26 (1) ◽  
pp. 57
Author(s):  
Zhi-Ling Zhu ◽  
Xiao-Dan Qiu ◽  
Shuo Wu ◽  
Yi-Tong Liu ◽  
Ting Zhao ◽  
...  
Keyword(s):  
Therapeutic Strategy ◽  
Blocking Effect ◽  
Spike Protein ◽  
Binding Affinities ◽  
The Novel ◽  
Converting Enzyme ◽  
Primary Method ◽  
Angiotensin Converting Enzyme 2 ◽  
Novel Coronavirus ◽  
Effective Drugs

The novel coronavirus disease (2019-nCoV) has been affecting global health since the end of 2019, and there is no sign that the epidemic is abating. Targeting the interaction between the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein and the human angiotensin-converting enzyme 2 (ACE2) receptor is a promising therapeutic strategy. In this study, surface plasmon resonance (SPR) was used as the primary method to screen a library of 960 compounds. A compound 02B05 (demethylzeylasteral, CAS number: 107316-88-1) that had high affinities for S-RBD and ACE2 was discovered, and binding affinities (KD, μM) of 02B05-ACE2 and 02B05-S-RBD were 1.736 and 1.039 μM, respectively. The results of a competition experiment showed that 02B05 could effectively block the binding of S-RBD to ACE2 protein. Furthermore, pseudovirus infection assay revealed that 02B05 could inhibit entry of SARS-CoV-2 pseudovirus into 293T cells to a certain extent at nontoxic concentration. The compoundobtained in this study serve as references for the design of drugs which have potential in the treatment of COVID-19 and can thus accelerate the process of developing effective drugs to treat SARS-CoV-2 infections.

scholarly journals ACE-2-derived Biomimetic Peptides for the Inhibition of Spike Protein of SARS-CoV-2

2020 ◽  
Author(s):  
Saroj Kumar Panda ◽  
Parth Sarthi Sen Gupta ◽  
Satyaranjan Biswal ◽  
Abhik Kumar Ray ◽  
Malay Kumar Rana
Keyword(s):  
Principal Component ◽  
Host Cells ◽  
Spike Protein ◽  
Peptide Inhibitor ◽  
The Novel ◽  
Receptor Binding Domain ◽  
Converting Enzyme ◽  
Inhibition Assay ◽  
Angiotensin Converting Enzyme 2 ◽  
Novel Coronavirus

<p>SARS-CoV-2, a novel coronavirus causing overwhelming death and infection worldwide, has emerged as a pandemic. Compared to its predecessor SARS-CoV, SARS-CoV-2 is more infective for being highly contagious and exhibiting tighter binding with host angiotensin-converting enzyme 2 (hACE-2). The entry of the virus into host cells is mediated by the interaction of its spike protein with hACE-2. Thus, a peptide that has a resemblance to hACE-2 but can overpower the spike protein-hACE-2 interaction will be a potential therapeutic to contain this virus. The non-interacting residues in the receptor-binding domain of hACE-2 have been mutated to generate a library of 136 new peptides. Out of this library, docking and virtual screening discover seven peptides that can exert a stronger interaction with the spike protein than hACE-2. A peptide derived from simultaneous mutation of all the non-interacting residues of hACE-2 yields two-fold stronger interaction than hACE-2 and thus turns out here to be the best peptide-inhibitor of the novel coronavirus. The binding of the spike protein and the best peptide-inhibitor with hACE-2 is explored further by molecular dynamics, free energy, and principal component analysis to demonstrate its efficacy. Further, the inhibition assay study with the best peptide inhibitor is in progress. </p>

scholarly journals An engineered stable mini-protein to plug SARS-Cov-2 Spikes

2020 ◽  
Author(s):  
Maria Romano ◽  
Alessia Ruggiero ◽  
Flavia Squeglia ◽  
Rita Berisio
Keyword(s):  
Viral Entry ◽  
Structural Data ◽  
Host Cells ◽  
Spike Protein ◽  
Helical Conformation ◽  
The Novel ◽  
Angiotensin Converting Enzyme 2 ◽  
Different Types ◽  
Novel Virus ◽  
High Yields

AbstractThe novel betacoronavirus SARS-CoV-2 is the etiological agent of the current pandemic COVID-19. Like other coronaviruses, this novel virus relies on the surface Spike glycoprotein to access the host cells, mainly through the interaction of its Receptor Binding Domain (RBD) with the human angiotensin-converting enzyme 2 (ACE2). Therefore, molecular entities able to interfere with binding of the SARS-CoV-2 Spike protein to ACE2 have a great potential to inhibit viral entry. Starting from the available structural data on the interaction between SARS-CoV-2 Spike protein and the host ACE2 receptor, we here engineered a mini-protein with the aim of creating a soluble and stable Spike interactor. This mini-protein, which was recombinantly produced in high yields, possesses a stable α helical conformation and is able to interact with the RBD of glycosylated Spike protein from SARS-CoV-2 with nanomolar affinity, as measured by microscale thermophoresis. By plugging the Spike protein, our mini-protein constitutes a valid tool for the development of treatments against different types of coronavirus.

scholarly journals Molecular basis of the logical evolution of the novel coronavirus SARS-CoV-2: A comparative analysis

2020 ◽  
Author(s):  
Abhisek Dwivedy ◽  
Krushna Chandra Murmu ◽  
Mohammed Ahmad ◽  
Punit Prasad ◽  
Bichitra Kumar Biswal ◽  
...  
Keyword(s):  
Molecular Basis ◽  
Conformational Flexibility ◽  
Spike Protein ◽  
The Novel ◽  
Amino Acid Residues ◽  
Evolutionary Pathway ◽  
Angiotensin Converting Enzyme 2 ◽  
Human Coronaviruses ◽  
Novel Coronavirus ◽  
Current Report

AbstractA novel disease, COVID-19, is sweeping the world since end of 2019. While in many countries, the first wave is over, but the pandemic is going through its next phase with a significantly higher infectability. COVID-19 is caused by the novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) that seems to be more infectious than any other previous human coronaviruses. To understand any unique traits of the virus that facilitate its entry into the host, we compared the published structures of the viral spike protein of SARS-CoV-2 with other known coronaviruses to determine the possible evolutionary pathway leading to the higher infectivity. The current report presents unique information regarding the amino acid residues that were a) conserved to maintain the binding with ACE2 (Angiotensin-converting enzyme 2), and b) substituted to confer an enhanced binding affinity and conformational flexibility to the SARS-CoV-2 spike protein. The present study provides novel insights into the evolutionary nature and molecular basis of higher infectability and perhaps the virulence of SARS-CoV-2.

scholarly journals A Review on Catastrophic Evolution of SARS-CoV to SARS-CoV2-A Global Pandemic

Coronaviruses ◽  
2020 ◽  
Vol 01 ◽  
Author(s):  
Sushmita Krishnan ◽  
Darshini Subramanian ◽  
Sri Sakthi Priyadarshini Rajamani
Keyword(s):  
The Novel ◽  
Angiotensin Converting Enzyme 2 ◽  
Global Pandemic ◽  
The Family ◽  
Natural Hosts ◽  
Current Outbreak ◽  
Global Statistics ◽  
Novel Coronavirus ◽  
And Control ◽  
Alternative Drugs

: The coronaviruses belonging to the family Coronaviridae have caused a massive pandemic in December 2019 af-ter its previous outbreaks as SARS-CoV and MERS. The outbreak is believed to have originated from the seafood and live market in Hubei province of China. The Rhinolophus species are the natural hosts of this virus. The unknown virus caus-ing pneumonia took away so many lives before recognising it as the novel Coronavirus. Very little information is known about the biology and nature of the current outbreak. This article reviews multiple aspects encompassing its origin, epide-miology, pathogenesis, symptoms and the global statistics of spread. Acute respiratory distress syndrome (ARDS) is the key symptom of this condition. Angiotensin converting enzyme 2 (ACE2) helps in the penetration of the virus into the tar-get cells. Deeper research and understanding is essential for identification of antibodies that inhibit ACE2 and can prevent viral replication. Drug design and control of disease is crucial. In countries like India where plant diversity is extensive, it is wise to focus on plant based alternative drugs. Many attempts have been made to review and curate the drug discovery attempts using immune-informatics and bioinformatics tools.

scholarly journals Computational Modeling Indicates A Decreased Affinity of SARS-CoV-2 to ACE2 by Steroids

2020 ◽  
Author(s):  
Alireza Mansouri ◽  
Rasoul Kowsar ◽  
Khaled Sadeghi ◽  
Akio Miyamoto
Keyword(s):  
Binding Free Energy ◽  
Spike Protein ◽  
The Novel ◽  
Angiotensin Converting Enzyme 2 ◽  
Risk Of Death ◽  
Main Protease ◽  
The World ◽  
Novel Coronavirus ◽  
Very High ◽  
Potential Use

Abstract The novel coronavirus disease (COVID-19) presently poses significant concerns around the world. Latest reports show that the degree of disease and mortality of COVID-19 infected patients may vary from gender to gender with a very high risk of death for seniors. It was hypothesized that sex steroid hormones estradiol (E2), progesterone (P4), testosterone (T), and dexamethasone (DEX) may change the interaction of coronavirus spike protein (CSP) with angiotensin converting enzyme-2 (ACE2). Data showed that E2 was more strongly to interact with the main protease of the coronavirus, while T had the lowest affinity for CSP. The binding energy of the CSP to ACE2 was increased in the presence of steroids; the greatest increase was observed by DEX and E2. The binding free energy of the CSP to ACE2 was the highest in the presence of E2 and DEX. Together, the interaction between CSP and ACE2 can be disrupted by E2 and to a greater extent by DEX, in part explaining the lower incidence of COVID-19 infection in women than men. The potential use of E2 and DEX to reduce coronavirus attachment to ACE2 in the early phase of the coronavirus invasion needs to be clinically investigated.

Angiotensin Converting Enzyme-2: A Doorway for SARS-CoV-2

Coronaviruses ◽  
2021 ◽  
Vol 02 ◽  
Author(s):  
Vikas Pandey ◽  
Indu Lata Kanwar ◽  
Tanweer Haider ◽  
Vishal Gour ◽  
Monika Vishwakarma ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Angiotensin Converting Enzyme ◽  
Human Body ◽  
Spike Protein ◽  
Specific Method ◽  
The Novel ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Novel Coronavirus

: The novel coronavirus severe acute respiratory syndrome Corona Virus-2 (SARS-CoV-2) has become a pandemic, as declared by WHO in March 2020 producing the deleterious effects to patients worldwide. The angiotensin-converting enzyme-2 (ACE-2) has been recognized as the co-receptor for SARS-CoV-2 infections and may acts as a therapeutic step in blocking the enzyme to reduce SARS-CoV-2 expression and further cellular entry. Presently, the role of ACE-2 in coronavirus disease 2019 (COVID-19) infection has been known and the experts have started working on the enzyme ACE-2 for the management and treatment of this pandemic disease. The binding of spike (S) protein of SARS-CoV-2 to these receptors is the most important step and plays a key role in viral replication, thus this enzyme is becoming the doorway for the entry and spread in the human body causing asymptomatic pneumonia and severe of which is leading to death. As no specific method to prevent and treat this disease is available, the use of ACE-2 as a targeting ligand with COVID-19 virus spike protein could be helpful in the proper management of SARS-CoV-2 pneumonia.

scholarly journals A miRNA-Peptide Fusion as a Vaccine Candidate Against the Novel Coronavirus (COVID-19). Exosomes as Potential Biomarkers of SARS-Cov-2 in Lung: After and Before Vaccination LCR_2020_b008-13

2020 ◽  
Keyword(s):  
In Silico ◽  
Vaccine Candidate ◽  
Unknown Etiology ◽  
The Novel ◽  
Preventive Vaccine ◽  
The Family ◽  
Novel Virus ◽  
Novel Coronavirus ◽  
First Time ◽  
Cancer Diseases

A new coronavirus named Covid-19 was reported in Wuhan, China in December 2019. The first time these cases were published they were classified as “pneumonia of unknown etiology”. The etiology of this illness is now attributed to a novel virus belonging to the coronavirus (CoV) family, COVID-19. Different from both MERS-CoV and SARS-CoV, 2019-nCoV it is the seventh member of the family of coronaviruses to infect humans. We have designed a preventive vaccine in Silico aimed to protect against Covid-19 infection and transmission. Our analysis identified 16 microRNA (miRNA) with theorical Exosome Affinity (EA) with peptide among 85.44-92.84 range. According to antiviral monitoring after and before vaccination using the candidate miRNA-peptide number 13 (LCR_2020_B008-13) with value EA=92.84 Ro. We proposed the exosomes as biomarkers of SARS-Covid-2 in lung: after and before vaccination. Due to, the miRNA-peptides, in Silico, manifesting highly affinity with exosomes, where our chimera LCR_2020_B008-13 could reach a representative activity against the Covid-19 virogenes due to “exosome sequestering”; and also, the treatment of cancer diseases due to “podosome depletion” in metastasis stage.

scholarly journals Structural Identification of the Electrostatic Hot Spots for Severe Acute Respiratory Syndrome Coronavirus Spike Protein to Be Complexed with Its Receptor ACE2 and Its Neutralizing Antibodies

2020 ◽  
Author(s):  
Wei Li
Keyword(s):  
Hot Spots ◽  
Neutralizing Antibodies ◽  
Complex Structure ◽  
Salt Bridge ◽  
Spike Protein ◽  
The Novel ◽  
Salt Bridges ◽  
Angiotensin Converting Enzyme 2 ◽  
Receptor Recognition ◽  
Novel Coronavirus

The spike protein of SARS coronavirus (SARS-CoV) attaches the virus to its cellular receptor, angiotensin-converting enzyme 2 (ACE2), which is mediated by the receptor binding domain (RBD) of the spike protein. Recently, an analysis based on decade-long structural studies of SARS was reported to illustrate with atomic-level details receptor recognition by the novel coronavirus from Wuhan, i.e., 2019-nCoV. Here, this article reports a comprehensive set of structural electrostatic analysis of all SARS-CoV spike protein RBD-related structures as of February 13, 2020, aiming at identifying the electrostatic hot spots for SARS-CoV spike protein to be complexed with ACE2 and its neutralizing antibodies. First, this article identified a structural action mechanism of the F26G19 antibody (of SARS-CoV spike protein), where its Asp56 residue binds to the Arg426 of the SARS-CoV spike protein RBD against the formation of the interfacial Arg426-Glu329 salt bridges between ACE2 and the SARS-CoV spike protein RBD. Second, a hypothesis is reported that a pair of electrostatic clips exist at the interface between ACE2 and the SARS-CoV spike protein RBD, including both Arg426-Glu329 and His445-Glu23-Lys447 salt bridges. Last, this article reports a structurally identified interfacial Glu35-Arg479 salt bridge which helps stabilize the complex structure of ACE2 and the SARS-CoV spike protein RBD. Overall, the structurally identified electrostatic hot spots reported here may be useful for the design of SARS-CoV-neutralizing antibodies in future.

scholarly journals ACE-2-derived Biomimetic Peptides for the Inhibition of Spike Protein of SARS-CoV-2

2020 ◽  
Author(s):  
Saroj Kumar Panda ◽  
Parth Sarthi Sen Gupta ◽  
Satyaranjan Biswal ◽  
Abhik Kumar Ray ◽  
Malay Kumar Rana
Keyword(s):  
Principal Component ◽  
Host Cells ◽  
Spike Protein ◽  
Peptide Inhibitor ◽  
The Novel ◽  
Receptor Binding Domain ◽  
Converting Enzyme ◽  
Inhibition Assay ◽  
Angiotensin Converting Enzyme 2 ◽  
Novel Coronavirus

<p>SARS-CoV-2, a novel coronavirus causing overwhelming death and infection worldwide, has emerged as a pandemic. Compared to its predecessor SARS-CoV, SARS-CoV-2 is more infective for being highly contagious and exhibiting tighter binding with host angiotensin-converting enzyme 2 (hACE-2). The entry of the virus into host cells is mediated by the interaction of its spike protein with hACE-2. Thus, a peptide that has a resemblance to hACE-2 but can overpower the spike protein-hACE-2 interaction will be a potential therapeutic to contain this virus. The non-interacting residues in the receptor-binding domain of hACE-2 have been mutated to generate a library of 136 new peptides. Out of this library, docking and virtual screening discover seven peptides that can exert a stronger interaction with the spike protein than hACE-2. A peptide derived from simultaneous mutation of all the non-interacting residues of hACE-2 yields two-fold stronger interaction than hACE-2 and thus turns out here to be the best peptide-inhibitor of the novel coronavirus. The binding of the spike protein and the best peptide-inhibitor with hACE-2 is explored further by molecular dynamics, free energy, and principal component analysis to demonstrate its efficacy. Further, the inhibition assay study with the best peptide inhibitor is in progress. </p>

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