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Temperature effect on the SARS-CoV-2: A molecular dynamics study of the spike homotrimeric glycoprotein.

ABSTRACT: Rapid spread of SARS-CoV-2 virus have boosted the need of knowledge about inactivation mechanisms to minimize the impact of COVID-19 pandemic. Recent studies have shown that SARS-CoV-2 virus can be disabled by heating, the exposure time for total inactivation depending on the reached temperature (e.g. more than 45 min at 329 K or less than 5 min at 373 K. In spite of recent crystallographic structures, little is known about the molecular changes induced by the temperature. Here, we unravel the molecular basis of the effect of the temperature over the SARS-CoV-2 spike glycoprotein, which is a homotrimer with three identical monomers, by executing atomistic molecular dynamics (MD) simulations at 298, 310, 324, 338, 358 and 373 K. Furthermore, both the closed down and open up conformational states, which affect the accessibility of receptor binding domain, have been considered. Our results suggest that the spike homotrimer undergoes drastic changes in the topology of the hydrogen bonding interactions and important changes on the secondary structure of the receptor binding domain (RBD), while electrostatic interactions (i.e. salt bridges) are mainly preserved. The proposed inactivation mechanism has important implications for engineering new approaches to fight the SARS-CoV-2 coronavirus, as for example, cleaving or reorganizing the hydrogen bonds through chaotropic agents or nanoparticles with local surface resonant plasmon effect.

SUBMITTER: Marti D

PROVIDER: S-EPMC8024222 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:COVID-19, a newly discovered type of coronavirus, is the cause of the pandemic infection that was first reported in Wuhan, China, in December 2019. One of the most critical problems in this regard is to identify innovative drugs that may reduce or manage this global health concern. Nanoparticles have shown a pivotal role in drug delivery systems in recent decades. The surface of nanoparticles could be covered by a layer composed of different biomolecules (e.g., proteins and macromolecules) following the incubation with a biological fluid. This protein-rich layer is called "Protein Corona." In this study, an all-atom molecular dynamics simulation was used for investigating the monomeric B domain of the spike glycoprotein due to its role in the accessibility of the spike glycoprotein to single-wall carbon nanotubes (SWCNTs). The interaction energy values between the carbon nanotube and B domain of the viral spike glycoprotein were evaluated. The obtained results, based on Lennard-Jones potentials, demonstrated that SWCNTs had an affinity to the B domain of the S1 subunit in the spike glycoprotein. The adsorption of SWCNTs on the B domain surface led to a significant change in solvent-accessible surface, internal hydrogen bonds, and finally in the tertiary structure, which could provide a reasonable method to impede the interaction between the angiotensin-converting enzyme II and SARS-CoV-2 spike glycoprotein. A decrease in the mean square displacement of the B domain was shown after the adsorption of SWCNTs as a result of increasing the hydrophobic-hydrophilic properties of the B domain. The arrangement of SWCNTs on the B domain surface and their interaction using the 2-acetamido-2-deoxy-β-d-glucopyranose group (988, 991, and 992) demonstrated that a change in the affinity of the S1 subunit could be used as a barrier to viral replication. The analysis of the SWCNT-B domain complex indicated that the presence of SWCNTs is able to cause alterations in the S1 subunit of the spike protein, and these nanotubes could be employed for further in-vitro and in-vivo antiviral studies. Also, SWCNTs are able to be utilized in drug delivery systems.

Project description:Purpose Viral diseases increasingly endanger the world public health because of the transient efficacy of antiviral therapies. The novel coronavirus disease 2019 (COVID-19) has been recently identified as caused by a new type of coronaviruses. This type of coronavirus binds to the human receptor through the Spike glycoprotein (S) Receptor Binding Domain (RBD). The spike protein is found in inaccessible (closed) or accessible (open) conformations in which the accessible conformation causes severe infection. Thus, this receptor is a significant target for antiviral drug design. Methods An attempt was made to recognize 111 natural and synthesized compounds in order to utilize them against SARS-CoV-2 spike glycoprotein to inhibit Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using simulation methods, such as molecular docking. The FAF-Drugs3, Pan-Assay Interference Compounds (PAINS), ADME (absorption, distribution, metabolism, excretion) databases along with Lipinski’s rules were used to evaluate the drug-like properties of the identified ligands. In order to analyze and identify the residues critical in the docking process of the spike glycoprotein, the interactions of proposed ligands with both conformations of the spike glycoprotein was simulated. Results The results showed that among the available ligands, seven ligands had significant interactions with the binding site of the spike glycoprotein, in which angiotensin-converting enzyme 2 (ACE2) is bounded. Out of seven candidate molecules, six ligands exhibited drug-like characteristics. The results also demonstrated that fluorophenyl and propane groups of ligands had optimal interactions with the binding site of the spike glycoprotein. Conclusion According to the results, our findings indicated the ability of six ligands to prevent the binding of the SARS-CoV-2 spike glycoprotein to its cognate receptor, providing novel compounds for the treatment of COVID-19. Supplementary Information The online version contains supplementary material available at 10.1007/s42600-020-00122-3.

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Temperature effect on the SARS-CoV-2: A molecular dynamics study of the spike homotrimeric glycoprotein.

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