scholarly journals Molecular mechanism of SARS-CoV-2 inactivation by temperature

2020 ◽  
Author(s):  
Didac Martí ◽  
Juan Torras ◽  
Oscar Betran ◽  
Pau Turon ◽  
Carlos Alemán
Keyword(s):  
Receptor Binding ◽  
Thermal Inactivation ◽  
Receptor Binding Domain ◽  
Salt Bridges ◽  
Hydrogen Bond Network ◽  
Conformational Variations ◽  
Inactivation Mechanism ◽  
Bond Network ◽  
Dynamics Simulations ◽  
Binding Subunit

AbstractRecent studies have shown that SARS-CoV-2 virus can be inactivated by effect of heat, even though, little is known about the molecular changes induced by the temperature. Here, we unravel the basics of such inactivation mechanism over the SARS-CoV-2 spike glycoprotein by executing atomistic molecular dynamics simulations. Both the closed down and open up states, which determine the accessibility to the receptor binding domain, were considered. Results suggest that the spike undergoes drastic changes in the topology of the hydrogen bond network while salt bridges are mainly preserved. Reorganization in the hydrogen bonds structure produces conformational variations in the receptor binding subunit and explain the thermal inactivation of the virus. Conversely, the macrostructure of the spike is preserved at high temperature because of the retained salt bridges. The proposed mechanism has important implications for engineering new approaches to inactivate the SARS-CoV-2 virus.

Reversible Hydrogen Bond Network Dynamics: Molecular Dynamics Simulations of Calix[4]arene-Catenanes

2011 ◽  
Vol 115 (20) ◽  
pp. 6445-6454 ◽  
Author(s):  
Thomas Schlesier ◽  
Thorsten Metzroth ◽  
Andreas Janshoff ◽  
Jürgen Gauss ◽  
Gregor Diezemann
Keyword(s):  
Molecular Dynamics ◽  
Hydrogen Bond ◽  
Molecular Dynamics Simulations ◽  
Network Dynamics ◽  
Hydrogen Bond Network ◽  
Bond Network ◽  
Dynamics Simulations

scholarly journals SARS-CoV-2, an evolutionary perspective of interaction with human ACE2 reveals undiscovered amino acids necessary for complex stability

2020 ◽  
Author(s):  
Vinicio Armijos-Jaramillo ◽  
Justin Yeager ◽  
Claire Muslin ◽  
Yunierkis Perez-Castillo
Keyword(s):  
Receptor Binding ◽  
Evolutionary Dynamics ◽  
Hot Spot ◽  
Critical Role ◽  
Human Cells ◽  
Binding Domain ◽  
Host Cells ◽  
Spike Protein ◽  
Receptor Binding Domain ◽  
Salt Bridges

AbstractThe emergence of SARS-CoV-2 has resulted in more than 200,000 infections and nearly 9,000 deaths globally so far. This novel virus is thought to have originated from an animal reservoir, and acquired the ability to infect human cells using the SARS-CoV cell receptor hACE2. In the wake of a global pandemic it is essential to improve our understanding of the evolutionary dynamics surrounding the origin and spread of a novel infectious disease. One way theory predicts selection pressures should shape viral evolution is to enhance binding with host cells. We first assessed evolutionary dynamics in select betacoronavirus spike protein genes to predict where these genomic regions are under directional or purifying selection between divergent viral lineages at various scales of relatedness. With this analysis, we determine a region inside the receptor-binding domain with putative sites under positive selection interspersed among highly conserved sites, which are implicated in structural stability of the viral spike protein and its union with human receptor hACE2. Next, to gain further insights into factors associated with coronaviruses recognition of the human host receptor, we performed modeling studies of five different coronaviruses and their potential binding to hACE2. Modeling results indicate that interfering with the salt bridges at hot spot 353 could be an effective strategy for inhibiting binding, and hence for the prevention of coronavirus infections. We also propose that a glycine residue at the receptor binding domain of the spike glycoprotein can have a critical role in permitting bat variants of the coronaviruses to infect human cells.

scholarly journals Computer Simulations of the interaction between SARS-CoV-2 spike glycoprotein and different surfaces

2020 ◽  
Author(s):  
David C. Malaspina ◽  
Jordi Faraudo
Keyword(s):  
Molecular Dynamics ◽  
Hydrogen Bonding ◽  
Receptor Binding ◽  
Hydrophobic Interactions ◽  
Prominent Feature ◽  
High Hydrogen ◽  
Binding Domains ◽  
Dynamics Simulations ◽  
Initial Adsorption ◽  
Binding Subunit

A prominent feature of coronaviruses is the presence of a large glycoprotein spike protruding from a lipidic membrane. This glycoprotein spike determines the interaction of coronaviruses with the environment and the host. In this paper, we perform all atomic Molecular Dynamics simulations of the interaction between the SARS-CoV-2 trimeric glycoprotein spike and surfaces of materials. We considered a material with high hydrogen bonding capacity (cellulose) and a material capable of strong hydrophobic interactions (graphite). Initially, the spike adsorbs to both surfaces through essentially the same residues belonging to the receptor binding subunit of its three monomers. Adsorption onto cellulose stabilizes in this configuration, with the help of a large number of hydrogen bonds developed between cellulose and the three receptor binding domains (RBD) of the glycoprotein spike. In the case of adsorption onto graphite, the initial adsorption configuration is not stable and the surface induces a substantial deformation of the glycoprotein spike with a large number of adsorbed residues not pertaining to the binding subunits of the spike monomers.

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.

How does hydrogen bond network analysis reveal the golden ratio of water–glycerol mixtures?

2020 ◽  
Vol 22 (5) ◽  
pp. 2887-2907
Author(s):  
Trevor R. Fisher ◽  
Guobing Zhou ◽  
Yijun Shi ◽  
Liangliang Huang
Keyword(s):  
Molecular Dynamics ◽  
Hydrogen Bond ◽  
Network Analysis ◽  
Molecular Dynamics Simulations ◽  
Golden Ratio ◽  
Hydrogen Bond Network ◽  
Maximum Contribution ◽  
Water Glycerol ◽  
Bond Network ◽  
Dynamics Simulations

Molecular dynamics simulations reveal that the maximum contribution of H-bonds between water and glycerol occurs around 30 mol% glycerol. Such a concentration is also where several of the mixture's properties have an observed maxima or minima.

scholarly journals Ethylene glycol revisited: Molecular dynamics simulations and visualization of the liquid and its hydrogen-bond network

2014 ◽  
Vol 189 ◽  
pp. 20-29 ◽  
Author(s):  
Alexander Kaiser ◽  
Oksana Ismailova ◽  
Antti Koskela ◽  
Stefan E. Huber ◽  
Marcel Ritter ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Hydrogen Bond ◽  
Ethylene Glycol ◽  
Molecular Dynamics Simulations ◽  
Hydrogen Bond Network ◽  
Bond Network ◽  
Dynamics Simulations

Study of the Hydrogen Bond Network in sub-and supercritical Water by Molecular Dynamics Simulations

2001 ◽  
Vol 56 (8) ◽  
pp. 579-584 ◽  
Author(s):  
S. Krishtal ◽  
M. Kiselev ◽  
Y. Puhovski ◽  
T. Kerdcharoen ◽  
S. Hannongbua ◽  
...  
Keyword(s):  
Hydrogen Bonds ◽  
Critical Point ◽  
Supercritical Water ◽  
Diffusion Coefficients ◽  
Md Simulations ◽  
Saturation Curve ◽  
Hydrogen Bond Network ◽  
Self Diffusion ◽  
Bond Network ◽  
Dynamics Simulations

Abstract For 12 points along the tangent to the saturation curve at the critical point the temperature dependen­cies of the heights of the first maximum in the 0 -0 RDF, the average number of hydrogen bonds, and the self-diffusion coefficients have been calculated from MD simulations. The curves of these three properties show an inflection near the critical point. To improve the understanding of these changes in going from subcritical to supercritical water the librational spectra and the change in the fractions of wa­ter molecules with a given number of hydrogen bonds as a function of temperature have been derived from the simulations, additionally.

scholarly journals A model for pH coupling of the SARS-CoV-2 spike protein open/closed equilibrium

2020 ◽  
Author(s):  
Jim Warwicker
Keyword(s):  
Cell Surface ◽  
Aspartic Acid ◽  
Receptor Binding ◽  
Ph Dependence ◽  
Salt Bridge ◽  
Spike Protein ◽  
Receptor Binding Domain ◽  
Salt Bridges ◽  
Heat Map ◽  
Human Coronaviruses

AbstractSARS-CoV-2, causative agent of the COVID-19 pandemic, is thought to release its RNA genome at either the cell surface or within endosomes, the balance being dependent on spike protein stability, and the complement of receptors, co-receptors and proteases. To investigate possible mediators of pH-dependence, pKa calculations have been made on a set of structures for spike protein ectodomain and fragments from SARS-CoV-2 and other coronaviruses. Dominating a heat map of the aggregated predictions, 3 histidine residues in S2 are consistently predicted as destabilising in pre-fusion (all 3) and post-fusion (2 of 3) structures. Other predicted features include the more moderate energetics of surface salt-bridge interactions, and sidechain-mainchain interactions. Two aspartic acid residues in partially buried salt-bridges have pKas that are calculated to be elevated and destabilising. Notably, the degree of destabilisation is predicted to vary between open and closed receptor binding domain conformations. It is therefore suggested that these groups contribute to a pH-dependence of the open/closed equilibrium. These observations are discussed in the context of SARS-CoV-2 infection, mutagenesis studies, and other human coronaviruses.

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