scholarly journals A computational study of the interface interaction between SARS-CoV-2 RBD and ACE2 from human, cat, dog and ferret.

2021 ◽  
Author(s):  
William Sote ◽  
Eduardo Franca ◽  
Aline Hora ◽  
Moacyr Comar
Keyword(s):  
Animal Species ◽  
Computational Study ◽  
Infection Process ◽  
Point Of View ◽  
Cellular Receptor ◽  
Angiotensin Converting Enzyme 2 ◽  
Dynamics Simulations ◽  
Key Residues ◽  
Total Impact

The total impact of the worldwide COVID-19 pandemic is still emerging, changing all relationships as a result, including those with pet animals. In the infection process, the use of Angiotensin-converting enzyme 2 (ACE2) as a cellular receptor to the spike protein of the new coronavirus is a fundamental step. In this sense, understanding which residue plays what role in the interaction between SARS-CoV-2 spike glycoprotein and ACE2 from cats, dogs, and ferrets is an important guide for helping to choose which animal model can be used to study the pathology of COVID-19 and if there are differences between these interactions and those occurring in the human system. Hence, trying to help to answer these questions, we performed classical molecular dynamics simulations to evaluate, from an atomistic point of view, the interactions in these systems. Our results show that there are significant differences in the interacting residues between the systems from different animal species, and the role of ACE2 key residues are different in each system and can assist in the search for different inhibitors for each animal.

scholarly journals Peptides presenting the binding site of human CD4 for the HIV-1 envelope glycoprotein gp120

2012 ◽  
Vol 8 ◽  
pp. 1858-1866 ◽  
Author(s):  
Julia Meier ◽  
Kristin Kassler ◽  
Heinrich Sticht ◽  
Jutta Eichler
Keyword(s):  
Amino Acids ◽  
Binding Site ◽  
Envelope Glycoprotein ◽  
Conformational Stability ◽  
Cellular Receptor ◽  
Binding Assays ◽  
Glycoprotein Gp120 ◽  
Dynamics Simulations ◽  
Key Residues ◽  
Hiv 1

Based on the structure of the HIV-1 glycoprotein gp120 in complex with its cellular receptor CD4, we have designed and synthesized peptides that mimic the binding site of CD4 for gp120. The ability of these peptides to bind to gp120 can be strongly enhanced by increasing their conformational stability through cyclization, as evidenced by binding assays, as well as through molecular-dynamics simulations of peptide–gp120 complexes. The specificity of the peptide–gp120 interaction was demonstrated by using peptide variants, in which key residues for the interaction with gp120 were replaced by alanine or D-amino acids.

scholarly journals Computational investigation on the role of C-Terminal of human albumin on the dimerization of Aβ1-42 peptide

2020 ◽  
Vol 10 (1) ◽  
pp. 4944-4955 ◽  
Keyword(s):  
Computational Study ◽  
Binding Free Energy ◽  
Conformational Dynamics ◽  
Human Albumin ◽  
Potential Of Mean Force ◽  
Amber Force Field ◽  
Aβ Aggregation ◽  
The Difference ◽  
Dynamics Simulations

Alzheimer’s disease (AD) is characterized by the presence of Amyloid-beta (Aβ) peptide, which has the propensity to fold into β-sheets under stress forming aggregated amyloid plaques. Nowadays many studies have focused on the development of novel, specific therapeutic strategies to slow down Aβ aggregation or control preformed aggregates. Albumin, the most abundant protein in the cerebrospinal fluid, was reported to bind Aβ impeding its aggregation. Recently, it has been reported that C-terminal (CTerm) of Human Albumin binds with Aβ1-42, impairs Aβ aggregation and promotes disassembly of Aβ aggregates protecting neurons. In this computational study, we have investigated the effect of CTerm on the conformational dynamics and the aggregation propensity of Aβ1-42 peptide. We have performed molecular dynamics simulations on the Aβ1-42-Aβ1-42 homodimer and Aβ1-42-CTerm of albumin heterodimer using the AMBER force field ff99SBildn. From the Potential of mean force (PMF) study and Binding free energy (BFE) analysis, we observed the association of Aβ1-42 peptide monomer with itself in the form of homodimer to be stronger than its association with the CTerm in the heterodimer complex. The difference in the number of residues in the Aβ1-42 peptide monomer (42 AAs) and CTerm (35 AAs) may be probable reason for the difference in association between the monomeric units in corresponding homodimer and heterodimer complexes. But even then CTerm shows a significant effect on the dimerization of Aβ1-42 peptide. Our findings therefore suggest that CTerm can be used for the disassembly of Aβ1-42 peptide monomer.

scholarly journals Neutralizing antibodies for the prevention and treatment of COVID-19

2021 ◽  
Author(s):  
Lanying Du ◽  
Yang Yang ◽  
Xiujuan Zhang
Keyword(s):  
Neutralizing Antibodies ◽  
Virus Entry ◽  
Infection Process ◽  
Cellular Receptor ◽  
Receptor Binding Domain ◽  
S Protein ◽  
Angiotensin Converting Enzyme 2 ◽  
Prevention And Treatment ◽  
Spectrum Activity ◽  
Broad Spectrum Activity

AbstractSevere acute respiratory syndrome coronavirus-2 (SARS-CoV-2) initiates the infection process by binding to the viral cellular receptor angiotensin-converting enzyme 2 through the receptor-binding domain (RBD) in the S1 subunit of the viral spike (S) protein. This event is followed by virus–cell membrane fusion mediated by the S2 subunit, which allows virus entry into the host cell. Therefore, the SARS-CoV-2 S protein is a key therapeutic target, and prevention and treatment of coronavirus disease 2019 (COVID-19) have focused on the development of neutralizing monoclonal antibodies (nAbs) that target this protein. In this review, we summarize the nAbs targeting SARS-CoV-2 proteins that have been developed to date, with a focus on the N-terminal domain and RBD of the S protein. We also describe the roles that binding affinity, neutralizing activity, and protection provided by these nAbs play in the prevention and treatment of COVID-19 and discuss the potential to improve nAb efficiency against multiple SARS-CoV-2 variants. This review provides important information for the development of effective nAbs with broad-spectrum activity against current and future SARS-CoV-2 strains.

scholarly journals Clinical determinants of coronavirus disease COVID-19 manifestation

HYPERTENSION ◽  
2021 ◽  
Vol 14 (5) ◽  
pp. 29-35
Author(s):  
O.M. Kovalyova
Keyword(s):  
Clinical Signs ◽  
Point Of View ◽  
Lung Damage ◽  
Angiotensin Converting Enzyme 2 ◽  
Virus Pneumonia ◽  
Infection Disease ◽  
Systemic Manifestations ◽  
Different Populations ◽  
The Relationship

The article presents the review of modern publications on the assessment of the factors which have impact on susceptibility, clinical course and outcomes of COVID-19 infection. Statistical data on rate of increased blood pressure and adverse clinical signs of infection disease in different populations are shown. The important role of angiotensin-converting enzyme 2 as functional cellular receptor for coronavirus and its participation in multiple systemic manifestations of COVID-19 are presented. The mechanisms of damage effects of cigarette smoking in virus pneumonia have been described. According to literature data, the relationship between metabolic disorders related to obesity and risk of severe coronavirus course is emphasized. From a pathophysiological point of view, an explanation is given for the occurrence of threatening complications in patients with a new coronavirus infection in the presence of diabetes mellitus — massive lung damage, acute respiratory distress syndrome, prothrombotic condition, venous and arterial thrombosis.

scholarly journals Computational study of the dissolution of cellulose into single chains: the role of the solvent and agitation

Cellulose ◽  
2022 ◽  
Author(s):  
Eivind Bering ◽  
Jonathan Ø. Torstensen ◽  
Anders Lervik ◽  
Astrid S. de Wijn
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Hydrophobic Interactions ◽  
Computational Study ◽  
Pure Water ◽  
Solvent Mixture ◽  
Dissolution Mechanism ◽  
Dynamics Simulations ◽  
External Forces

Abstract We investigate the dissolution mechanism of cellulose using molecular dynamics simulations in both water and a mixture solvent consisting of water with Na$$^+$$ + , OH$$^-$$ - and urea. As a first computational study of its kind, we apply periodic external forces that mimic agitation of the suspension. Without the agitation, the bundles do not dissolve, neither in water nor solvent. In the solvent mixture the bundle swells with significant amounts of urea entering the bundle, as well as more water than in the bundles subjected to pure water. We also find that the mixture solution stabilizes cellulose sheets, while in water these immediately collapse into bundles. Under agitation the bundles dissolve more easily in the solvent mixture than in water, where sheets of cellulose remain that are bound together through hydrophobic interactions. Our findings highlight the importance of urea in the solvent, as well as the hydrophobic interactions, and are consistent with experimental results. Graphical abstract

scholarly journals A Theoretical Approach to Demystify the Role of Copper Salts and O2 in the Mechanism of C-N Bond Cleavage and Nitrogen Transfer

2021 ◽  
Author(s):  
Boyli Ghosh ◽  
Ambar Banerjee ◽  
Lisa Roy ◽  
Rounak Nath ◽  
Rabindra Nath Manna Manna ◽  
...  
Keyword(s):  
Computational Study ◽  
Bond Cleavage ◽  
Nitrogen Transfer ◽  
Copper Salts ◽  
Cyanide Anion ◽  
Aryl Aldehydes ◽  
Bond Scission ◽  
Dynamics Simulations ◽  
Experimental Findings

<b>C≡N bond scission accomplished by protonation, reductive cleavage and metathesis techniques are well-known to execute nitrogen transfer reactions. Herein, we have conducted an extensive computational study, using DFT and molecular dynamics simulations, to unravel the mechanistic pathways traversed in CuCN and CuBr<sub>2</sub> promoted splitting of coordinated cyanide anion under a dioxygen atmosphere, which enables nitrogen transfer to various aldehydes. Our detailed electronic structure analysis using <i>ab initio</i> multi-reference CASSCF calculations reveal that both the promoters facilitate radical pathways, in agreement with the experimental findings. This is a unique instance of oxygen activation initiated by single electron transfer from the nitrile carbon, while the major driving force is the operation of the Cu<sup>II/I </sup>redox cycle. Our study reveals that the copper salts act as the “electron pool” in this unique nitrogen transfer reaction forming aryl nitrile from aryl aldehydes.</b><br>

scholarly journals A Theoretical Approach to Demystify the Role of Copper Salts and O2 in the Mechanism of C-N Bond Cleavage and Nitrogen Transfer

2021 ◽  
Author(s):  
Boyli Ghosh ◽  
Ambar Banerjee ◽  
Lisa Roy ◽  
Rounak Nath ◽  
Rabindra Nath Manna Manna ◽  
...  
Keyword(s):  
Computational Study ◽  
Bond Cleavage ◽  
Nitrogen Transfer ◽  
Copper Salts ◽  
Cyanide Anion ◽  
Aryl Aldehydes ◽  
Bond Scission ◽  
Dynamics Simulations ◽  
Experimental Findings

<b>C≡N bond scission accomplished by protonation, reductive cleavage and metathesis techniques are well-known to execute nitrogen transfer reactions. Herein, we have conducted an extensive computational study, using DFT and molecular dynamics simulations, to unravel the mechanistic pathways traversed in CuCN and CuBr<sub>2</sub> promoted splitting of coordinated cyanide anion under a dioxygen atmosphere, which enables nitrogen transfer to various aldehydes. Our detailed electronic structure analysis using <i>ab initio</i> multi-reference CASSCF calculations reveal that both the promoters facilitate radical pathways, in agreement with the experimental findings. This is a unique instance of oxygen activation initiated by single electron transfer from the nitrile carbon, while the major driving force is the operation of the Cu<sup>II/I </sup>redox cycle. Our study reveals that the copper salts act as the “electron pool” in this unique nitrogen transfer reaction forming aryl nitrile from aryl aldehydes.</b><br>

scholarly journals Beyond Shielding: The Roles of Glycans in SARS-CoV-2 Spike Protein

2020 ◽  
Author(s):  
Lorenzo Casalino ◽  
Zied Gaieb ◽  
Jory A. Goldsmith ◽  
Christy K. Hjorth ◽  
Abigail C. Dommer ◽  
...  
Keyword(s):  
Vaccine Development ◽  
Conformational Dynamics ◽  
Biological Data ◽  
S Protein ◽  
Angiotensin Converting Enzyme 2 ◽  
Conformational Plasticity ◽  
Host Cell Entry ◽  
Dynamics Simulations ◽  
Structural Insights

AbstractThe ongoing COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in more than 15,000,000 infections and 600,000 deaths worldwide to date. Antibody development efforts mainly revolve around the extensively glycosylated SARS-CoV-2 spike (S) protein, which mediates the host cell entry by binding to the angiotensin-converting enzyme 2 (ACE2). Similar to many other viruses, the SARS-CoV-2 spike utilizes a glycan shield to thwart the host immune response. Here, we built a full-length model of glycosylated SARS-CoV-2 S protein, both in the open and closed states, augmenting the available structural and biological data. Multiple microsecond-long, all-atom molecular dynamics simulations were used to provide an atomistic perspective on the roles of glycans, and the protein structure and dynamics. We reveal an essential structural role of N-glycans at sites N165 and N234 in modulating the conformational dynamics of the spike’s receptor binding domain (RBD), which is responsible for ACE2 recognition. This finding is corroborated by biolayer interferometry experiments, which show that deletion of these glycans through N165A and N234A mutations significantly reduces binding to ACE2 as a result of the RBD conformational shift towards the “down” state. Additionally, end-to-end accessibility analyses outline a complete overview of the vulnerabilities of the glycan shield of SARS-CoV-2 S protein, which may be exploited by therapeutic efforts targeting this molecular machine. Overall, this work presents hitherto unseen functional and structural insights into the SARS-CoV-2 S protein and its glycan coat, providing a strategy to control the conformational plasticity of the RBD that could be harnessed for vaccine development.

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