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 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 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.

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.

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 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>

scholarly journals Genetic Variation and Evolution of the 2019 Novel Coronavirus

2021 ◽  
pp. 1-13
Author(s):  
Salvatore Dimonte ◽  
Muhammed Babakir-Mina ◽  
Taib Hama-Soor ◽  
Salar Ali
Keyword(s):  
Amino Acid ◽  
Receptor Binding ◽  
Rapid Evolution ◽  
Single Amino Acid ◽  
Angiotensin Converting Enzyme 2 ◽  
New Type ◽  
Amino Acid Mutations ◽  
Host Infection ◽  
Human Coronaviruses ◽  
Novel Coronavirus

<b><i>Introduction:</i></b> SARS-CoV-2 is a new type of coronavirus causing a pandemic severe acute respiratory syndrome (SARS-2). Coronaviruses are very diverting genetically and mutate so often periodically. The natural selection of viral mutations may cause host infection selectivity and infectivity. <b><i>Methods:</i></b> This study was aimed to indicate the diversity between human and animal coronaviruses through finding the rate of mutation in each of the spike, nucleocapsid, envelope, and membrane proteins. <b><i>Results:</i></b> The mutation rate is abundant in all 4 structural proteins. The most number of statistically significant amino acid mutations were found in spike receptor-binding domain (RBD) which may be because it is responsible for a corresponding receptor binding in a broad range of hosts and host selectivity to infect. Among 17 previously known amino acids which are important for binding of spike to angiotensin-converting enzyme 2 (ACE2) receptor, all of them are conservative among human coronaviruses, but only 3 of them significantly are mutated in animal coronaviruses. A single amino acid aspartate-454, that causes dissociation of the RBD of the spike and ACE2, and F486 which gives the strength of binding with ACE2 remain intact in all coronaviruses. <b><i>Discussion/Conclusion:</i></b> Observations of this study provided evidence of the genetic diversity and rapid evolution of SARS-CoV-2 as well as other human and animal coronaviruses.

scholarly journals ACE2 Nascence, trafficking, and SARS-CoV-2 pathogenesis: the saga continues

2021 ◽  
Vol 15 (1) ◽  
Author(s):  
Sally Badawi ◽  
Bassam R. Ali
Keyword(s):  
Cell Surface ◽  
Angiotensin Converting Enzyme ◽  
The Novel ◽  
Converting Enzyme ◽  
Post Translational Modifications ◽  
Angiotensin Converting Enzyme 2 ◽  
Viral Attachment ◽  
Novel Coronavirus ◽  
Effective Medication ◽  
Potential Use

AbstractWith the emergence of the novel coronavirus SARS-CoV-2 since December 2019, more than 65 million cases have been reported worldwide. This virus has shown high infectivity and severe symptoms in some cases, leading to over 1.5 million deaths globally. Despite the collaborative and concerted research efforts that have been made, no effective medication for COVID-19 (coronavirus disease-2019) is currently available. SARS-CoV-2 uses the angiotensin-converting enzyme 2 (ACE2) as an initial mediator for viral attachment and host cell invasion. ACE2 is widely distributed in the human tissues including the cell surface of lung cells which represent the primary site of the infection. Inhibiting or reducing cell surface availability of ACE2 represents a promising therapy for tackling COVID-19. In this context, most ACE2–based therapeutic strategies have aimed to tackle the virus through the use of angiotensin-converting enzyme (ACE) inhibitors or neutralizing the virus by exogenous administration of ACE2, which does not directly aim to reduce its membrane availability. However, through this review, we present a different perspective focusing on the subcellular localization and trafficking of ACE2. Membrane targeting of ACE2, and shedding and cellular trafficking pathways including the internalization are not well elucidated in literature. Therefore, we hereby present an overview of the fate of newly synthesized ACE2, its post translational modifications, and what is known of its trafficking pathways. In addition, we highlight the possibility that some of the identified ACE2 missense variants might affect its trafficking efficiency and localization and hence may explain some of the observed variable severity of SARS-CoV-2 infections. Moreover, an extensive understanding of these processes is necessarily required to evaluate the potential use of ACE2 as a credible therapeutic target.

scholarly journals Synthesis and immunological evaluation of synthetic peptide based anti-SARS-CoV-2 vaccine candidates

2021 ◽  
Author(s):  
Qingyu Zhao ◽  
Yanan Gao ◽  
Min Xiao ◽  
Xuefei Huang ◽  
Xuanjun Wu
Keyword(s):  
Synthetic Peptide ◽  
Spike Protein ◽  
Effective Vaccine ◽  
The Novel ◽  
Vaccine Candidates ◽  
Peptide Epitopes ◽  
Novel Coronavirus ◽  
Immunological Evaluation

For prevention of the coronavirus disease 2019 caused by the novel coronavirus SARS-CoV-2, an effective vaccine is critical. Herein, several potential peptide epitopes from the spike protein of SARS-CoV-2 have...

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