Three-Dimensional Structural Stability and Local Electrostatic Potential at Point Mutations in Spike Protein of SARS-CoV-2 Coronavirus

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(4), P. 2174 - 2174

Published: Feb. 11, 2024

The contagiousness of SARS-CoV-2 β-coronavirus is determined by the virus–receptor electrostatic association its positively charged spike (S) protein with negatively angiotensin converting enzyme-2 (ACE2 receptor) epithelial cells. If some mutations occur, potential on surface receptor-binding domain (RBD) could be altered, and S-ACE2 become stronger or weaker. aim current research to investigate whether point can noticeably alter RBD 3D stability S1-subunit S-protein. For this purpose, 15 mutants different hydrophilicity electric charge (positive, negative, uncharged) substituted substituting amino acid residues, located at S1-ACE2 interface, are selected, structure reconstructed base crystallographic S-protein wild-type strain sequence unfolded polypeptide chain mutants. Then, Gibbs free energy folding, isoelectric point, pH-dependent computed using programs for electrostatics. results show alterations in local vicinity mutant residue, which influence association. This approach allows prediction relative infectivity, transmissibility, (at equal social immune status) new reconstruction calculation potential.

Language: Английский

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Effect of Delta and Omicron Mutations on the RBD-SD1 Domain of the Spike Protein in SARS-CoV-2 and the Omicron Mutations on RBD-ACE2 Interface Complex

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(17), P. 10091 - 10091

Published: Sept. 3, 2022

The receptor-binding domain (RBD) is the essential part in Spike-protein (S-protein) of SARS-CoV-2 virus that directly binds to human ACE2 receptor, making it a key target for many vaccines and therapies. Therefore, any mutations at this could affect efficacy these treatments as well viral-cell entry mechanism. We introduce ab initio DFT-based computational study mainly focuses on two parts: (1) Mutations effects both Delta Omicron variants RBD-SD1 domain. (2) Impact RBD structure properties RBD-ACE2 interface system. in-depth analysis based novel concept amino acid-amino acid bond pair units (AABPU) reveal differences between and/or its corresponding wild-type strain terms role played by non-local interactions, their 3D shapes sizes, contribution hydrogen bonding partial charge distributions. Our results also show interaction with significantly increased acids providing information implications penetration S-protein into ACE2, thus offering possible explanation high infectivity. findings enable us present, more conspicuous atomic level detail, effect specific may help predicting mitigating next variant concern.

Language: Английский

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SARS-CoV-2 Omicron XBB lineage spike structures, conformations, antigenicity, and receptor recognition

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Feb. 13, 2024

A recombinant lineage of the SARS-CoV-2 Omicron variant, named XBB, appeared in late 2022 and evolved descendants that successively swept local global populations. XBB members were noted for their improved immune evasion transmissibility. Here, we determine cryo-EM structures XBB.1.5, XBB.1.16, EG.5 EG.5.1 spike (S) ectodomains to reveal reinforced 3-RBD-down receptor inaccessible closed states mediated by interprotomer binding domain (RBD) interactions previously observed BA.1 BA.2. Improved XBB.1.5 XBB.1.16 RBD stability compensated loss caused early mutations, while F456L substitution reduced stability. S1 subunit mutations had long-range impacts on conformation epitope presentation S2 subunit. Our results continued S protein evolution via simultaneous optimization multiple parameters including stability, evasion, dramatic effects relatively few residue substitutions altering conformational landscape.

Language: Английский

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Correlating the differences in the receptor binding domain of SARS-CoV-2 spike variants on their interactions with human ACE2 receptor

Scientific Reports, Journal Year: 2023, Volume and Issue: 13(1)

Published: May 30, 2023

Spike glycoprotein of SARS-CoV-2 variants plays a critical role in infection and transmission through its interaction with human angiotensin converting enzyme 2 (hACE2) receptors. Prior findings using molecular docking biomolecular studies reported varied on the difference interactions among spike hACE2 Hence, it is prerequisite to understand these more precise manner. To this end, firstly, we performed ELISA trimeric glycoproteins including Wuhan Hu-1(Wild), Delta, C.1.2 Omicron. Further, study specific manner by mimicking natural infection, developed receptors expressing HEK-293T cell line, evaluated their binding efficiencies competitive D614G pseudotyped virus. In line existing findings, observed that Omicron had higher efficiency compared Delta both Cellular models. Intriguingly, found cellular models could differentiate subtle differences between closely related Our model provides method evaluate sub-lineages

Language: Английский

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Localized delivery of nanomedicine and antibodies for combating COVID-19

Acta Pharmaceutica Sinica B, Journal Year: 2022, Volume and Issue: 13(5), P. 1828 - 1846

Published: Sept. 23, 2022

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has been a major health burden in the world. So far, many strategies have investigated to control spread of COVID-19, including social distancing, disinfection protocols, vaccines, and antiviral treatments. Despite significant achievement, due constantly emerging new variants, COVID-19 is still great challenge global healthcare system. It an urgent demand for development therapeutics technologies containing wild SARS-CoV-2. Inhaled administration useful treatment lung diseases, enables drugs reach site action directly with benefits decreased dose, improved safety, enhanced patient compliance. Nanotechnology extensively applied prevention COVID-19. In this review, inhaled nanomedicines antibodies, as well intranasal nanodrugs, are summarized.

Language: Английский

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