Structural analysis of novel amino acid substitutions in SARS-CoV-2 spike protein receptor-binding domain

Burcu Biterge Süt

doi:10.15671/hjbc.776430

Research Article

Year 2021, Issue: 4, 367 - 374, 25.05.2021

Burcu Biterge Süt

https://doi.org/10.15671/hjbc.776430

Abstract

Project Number

None

References

1. Q. Li, X. Guan, P. Wu, X. Wang, L. Zhou, Y. Tong et al. Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus-Infected Pneumonia. N Engl J Med. 382(2020):1199-1207. doi:10.1056/NEJMoa2001316.
2. P.S. Masters. The molecular biology of coronaviruses. Adv Virus Res. 66 (2006) 193-292. doi:10.1016/S0065-3527(06)66005-3.
3. C. Drosten, S. Günther, W. Preiser, S. van der Werf, H.R. Brodt, S. Becker et al. Identification of a novel coronavirus associated with severe acute respiratory syndrome. N Engl J Med. 348 (2003) 1967-1976.
4. J. Zheng. SARS-CoV-2: an Emerging Coronavirus that Causes a Global Threat. Int J Biol Sci. 16 (2020) 1678-1685. doi:10.7150/ijbs.45053.
5. D.E. Gordon, G.M. Jang, M. Bouhaddou, J. Xu, K. Obernier, K.M. White et al. A SARS-CoV-2 protein interaction map reveals targets for drug repurposing [published online ahead of print]. Nature. (2020) doi:10.1038/s41586-020-2286-9.
6. H. Zhang, J.M. Penninger, Y. Li, N. Zhong, A.S. Slutsky. Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: molecular mechanisms and potential therapeutic target. Intensive Care Med. 46 (2020) 586-590. doi:10.1007/s00134-020-05985-9.
7. G. Simmons, P. Zmora, S. Gierer, A. Heurich, S. Pöhlmann. Proteolytic activation of the SARS-coronavirus spike protein: cutting enzymes at the cutting edge of antiviral research. Antiviral Res. 100 (2013) 605-614. doi:10.1016/j.antiviral.2013.09.028.
8. J. Lan, J. Ge, J. Yu, S. Shan, H. Zhou, S. Fan, et al. Crystal structure of the 2019-nCoVspike receptor-binding domain bound with the ACE2 receptor. J BioRxiv (2020) http://doi.org/10.1101/2020.02.19.956235%JbioRxiv.
9. W.E. Chan, C.K. Chuang, S.H. Yeh, M.S. Chang, S.S. Chen. Functional characterization of heptad repeat 1 and 2 mutants of the spike protein of severe acute respiratory syndrome coronavirus. J Virol. 80 (2006) 3225-3237. doi:10.1128/JVI.80.7.3225-3237.2006.
10. G. Salvatori, L. Luberto, M. Maffei, L. Aurisicchio, G. Roscilli, F. Palombo et al. SARS-CoV-2 SPIKE PROTEIN: an optimal immunological target for vaccines. J Transl Med. 18 (2020) 222. doi:10.1186/s12967-020-02392-y.
11. D. Benvenuto, M. Giovanetti, A. Ciccozzi, S. Spoto, S. Angeletti, M. Ciccozzi. The 2019-new coronavirus epidemic: Evidence for virus evolution. J Med Virol. 92 (2020) 455-459. doi:10.1002/jmv.25688.
12. F. Sievers, A. Wilm, D. Dineen, T.J. Gibson, K. Karplus, W. Li, et al. Fast, scalable generation of high-quality protein multiple sequence alignments using Clustal Omega. Mol Syst Biol. 7 (2011) 539. doi: 10.1038/msb.2011.75.
13. Y. Zhang. I-TASSER server for protein 3D structure prediction. BMC Bioinformatics. 9 (2008) 40. doi:10.1186/1471-2105-9-40.
14. E.F. Pettersen, T.D. Goddard, C.C. Huang, G.S. Couch, D.M. Greenblatt, E.C. Meng et al. UCSF Chimera--a visualization system for exploratory research and analysis. J Comput Chem. 25 (2004) 1605-1612. doi:10.1002/jcc.20084.
15. B. Shanmugaraj, K. Siriwattananon, K. Wangkanont, W. Phoolcharoen. Perspectives on monoclonal antibody therapy as potential therapeutic intervention for Coronavirus disease-19 (COVID-19). Asian Pac J Allergy Immunol. 38 (2020) 10-18. doi:10.12932/AP-200220-0773.
16. J. Shang, G. Ye, K. Shi, Y. Wan, C. Luo, H. Aihara et al. Structural basis of receptor recognition by SARS-CoV-2. Nature. 581(2020) 221-224. doi:10.1038/s41586-020-2179-y.
17. J.T. Ortega, M.L. Serrano, F.H. Pujol, H.R. Rangel. Role of changes in SARS-CoV-2 spike protein in the interaction with the human ACE2 receptor: an in silico analysis. EXCLI J. 19 (2020) 410-417. doi:10.17179/excli2020-1167.
18. C. Garcia-Iriepa, C. Hognon, A. Francés-Monerris, I. Iriepa, T. Miclot, G. Barone, et al. Thermodynamics of the Interaction Between SARS-CoV-2 Spike Protein and Human ACE2 Receptor. Effects of Possible Ligands. ChemRxiv. (2020) https://doi.org/10.26434/chemrxiv.12186624.v2.
19. G.A. Versteeg, P.S. van de Nes, P.J. Bredenbeek, W.J. Spaan. The coronavirus spike protein induces endoplasmic reticulum stress and upregulation of intracellular chemokine mRNA concentrations. J Virol. 81 (2007) 10981-10990. doi:10.1128/JVI.01033-07.

Structural analysis of novel amino acid substitutions in SARS-CoV-2 spike protein receptor-binding domain

Year 2021, Issue: 4, 367 - 374, 25.05.2021

Burcu Biterge Süt

https://doi.org/10.15671/hjbc.776430

Abstract

There are several novel amino acid substitutions in SARS-CoV-2 spike protein, which could account for the increased infectivity of this newly emerged virus. Therefore, in this paper we aimed to evaluate the potential effects of these amino acid substitutions on protein structure and function. For this purpose, we made use of several state-of-the-art computational tools and performed in silico analyses on protein similarity, 2D and 3D structure, ligand binding and biological function. We found that some of the novel amino acid changes caused significant structural alterations both at the secondary and tertiary structure level, possibly affecting the interaction between the spike protein receptor-binding domain (RBD) and ACE2, as well as other ligands. In conclusion, data we provided here is a significant contribution to our current knowledge of the SARS-CoV-2 virus and will aid in having a better understanding of its molecular differences, mechanism of infection and the cellular processes it affects in the host in order to develop better therapies and vaccines.

Keywords

COVID-19, coronavirus, SARS-CoV-2, spike protein, RBD

Supporting Institution

None

Project Number

None

Thanks

None

References

1. Q. Li, X. Guan, P. Wu, X. Wang, L. Zhou, Y. Tong et al. Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus-Infected Pneumonia. N Engl J Med. 382(2020):1199-1207. doi:10.1056/NEJMoa2001316.
2. P.S. Masters. The molecular biology of coronaviruses. Adv Virus Res. 66 (2006) 193-292. doi:10.1016/S0065-3527(06)66005-3.
3. C. Drosten, S. Günther, W. Preiser, S. van der Werf, H.R. Brodt, S. Becker et al. Identification of a novel coronavirus associated with severe acute respiratory syndrome. N Engl J Med. 348 (2003) 1967-1976.
4. J. Zheng. SARS-CoV-2: an Emerging Coronavirus that Causes a Global Threat. Int J Biol Sci. 16 (2020) 1678-1685. doi:10.7150/ijbs.45053.
5. D.E. Gordon, G.M. Jang, M. Bouhaddou, J. Xu, K. Obernier, K.M. White et al. A SARS-CoV-2 protein interaction map reveals targets for drug repurposing [published online ahead of print]. Nature. (2020) doi:10.1038/s41586-020-2286-9.
6. H. Zhang, J.M. Penninger, Y. Li, N. Zhong, A.S. Slutsky. Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: molecular mechanisms and potential therapeutic target. Intensive Care Med. 46 (2020) 586-590. doi:10.1007/s00134-020-05985-9.
7. G. Simmons, P. Zmora, S. Gierer, A. Heurich, S. Pöhlmann. Proteolytic activation of the SARS-coronavirus spike protein: cutting enzymes at the cutting edge of antiviral research. Antiviral Res. 100 (2013) 605-614. doi:10.1016/j.antiviral.2013.09.028.
8. J. Lan, J. Ge, J. Yu, S. Shan, H. Zhou, S. Fan, et al. Crystal structure of the 2019-nCoVspike receptor-binding domain bound with the ACE2 receptor. J BioRxiv (2020) http://doi.org/10.1101/2020.02.19.956235%JbioRxiv.
9. W.E. Chan, C.K. Chuang, S.H. Yeh, M.S. Chang, S.S. Chen. Functional characterization of heptad repeat 1 and 2 mutants of the spike protein of severe acute respiratory syndrome coronavirus. J Virol. 80 (2006) 3225-3237. doi:10.1128/JVI.80.7.3225-3237.2006.
10. G. Salvatori, L. Luberto, M. Maffei, L. Aurisicchio, G. Roscilli, F. Palombo et al. SARS-CoV-2 SPIKE PROTEIN: an optimal immunological target for vaccines. J Transl Med. 18 (2020) 222. doi:10.1186/s12967-020-02392-y.
11. D. Benvenuto, M. Giovanetti, A. Ciccozzi, S. Spoto, S. Angeletti, M. Ciccozzi. The 2019-new coronavirus epidemic: Evidence for virus evolution. J Med Virol. 92 (2020) 455-459. doi:10.1002/jmv.25688.
12. F. Sievers, A. Wilm, D. Dineen, T.J. Gibson, K. Karplus, W. Li, et al. Fast, scalable generation of high-quality protein multiple sequence alignments using Clustal Omega. Mol Syst Biol. 7 (2011) 539. doi: 10.1038/msb.2011.75.
13. Y. Zhang. I-TASSER server for protein 3D structure prediction. BMC Bioinformatics. 9 (2008) 40. doi:10.1186/1471-2105-9-40.
14. E.F. Pettersen, T.D. Goddard, C.C. Huang, G.S. Couch, D.M. Greenblatt, E.C. Meng et al. UCSF Chimera--a visualization system for exploratory research and analysis. J Comput Chem. 25 (2004) 1605-1612. doi:10.1002/jcc.20084.
15. B. Shanmugaraj, K. Siriwattananon, K. Wangkanont, W. Phoolcharoen. Perspectives on monoclonal antibody therapy as potential therapeutic intervention for Coronavirus disease-19 (COVID-19). Asian Pac J Allergy Immunol. 38 (2020) 10-18. doi:10.12932/AP-200220-0773.
16. J. Shang, G. Ye, K. Shi, Y. Wan, C. Luo, H. Aihara et al. Structural basis of receptor recognition by SARS-CoV-2. Nature. 581(2020) 221-224. doi:10.1038/s41586-020-2179-y.
17. J.T. Ortega, M.L. Serrano, F.H. Pujol, H.R. Rangel. Role of changes in SARS-CoV-2 spike protein in the interaction with the human ACE2 receptor: an in silico analysis. EXCLI J. 19 (2020) 410-417. doi:10.17179/excli2020-1167.
18. C. Garcia-Iriepa, C. Hognon, A. Francés-Monerris, I. Iriepa, T. Miclot, G. Barone, et al. Thermodynamics of the Interaction Between SARS-CoV-2 Spike Protein and Human ACE2 Receptor. Effects of Possible Ligands. ChemRxiv. (2020) https://doi.org/10.26434/chemrxiv.12186624.v2.
19. G.A. Versteeg, P.S. van de Nes, P.J. Bredenbeek, W.J. Spaan. The coronavirus spike protein induces endoplasmic reticulum stress and upregulation of intracellular chemokine mRNA concentrations. J Virol. 81 (2007) 10981-10990. doi:10.1128/JVI.01033-07.

There are 19 citations in total.

Details

Primary Language	English
Subjects	Engineering
Journal Section	Research Article
Authors	Burcu Biterge Süt 0000-0001-5756-5756
Project Number	None
Publication Date	May 25, 2021
Acceptance Date	February 25, 2021
Published in Issue	Year 2021 Issue: 4

Cite

APA	Biterge Süt, B. (2021). Structural analysis of novel amino acid substitutions in SARS-CoV-2 spike protein receptor-binding domain. Hacettepe Journal of Biology and Chemistry, 49(4), 367-374. https://doi.org/10.15671/hjbc.776430
AMA	Biterge Süt B. Structural analysis of novel amino acid substitutions in SARS-CoV-2 spike protein receptor-binding domain. HJBC. May 2021;49(4):367-374. doi:10.15671/hjbc.776430
Chicago	Biterge Süt, Burcu. “Structural Analysis of Novel Amino Acid Substitutions in SARS-CoV-2 Spike Protein Receptor-Binding Domain”. Hacettepe Journal of Biology and Chemistry 49, no. 4 (May 2021): 367-74. https://doi.org/10.15671/hjbc.776430.
EndNote	Biterge Süt B (May 1, 2021) Structural analysis of novel amino acid substitutions in SARS-CoV-2 spike protein receptor-binding domain. Hacettepe Journal of Biology and Chemistry 49 4 367–374.
IEEE	B. Biterge Süt, “Structural analysis of novel amino acid substitutions in SARS-CoV-2 spike protein receptor-binding domain”, HJBC, vol. 49, no. 4, pp. 367–374, 2021, doi: 10.15671/hjbc.776430.
ISNAD	Biterge Süt, Burcu. “Structural Analysis of Novel Amino Acid Substitutions in SARS-CoV-2 Spike Protein Receptor-Binding Domain”. Hacettepe Journal of Biology and Chemistry 49/4 (May 2021), 367-374. https://doi.org/10.15671/hjbc.776430.
JAMA	Biterge Süt B. Structural analysis of novel amino acid substitutions in SARS-CoV-2 spike protein receptor-binding domain. HJBC. 2021;49:367–374.
MLA	Biterge Süt, Burcu. “Structural Analysis of Novel Amino Acid Substitutions in SARS-CoV-2 Spike Protein Receptor-Binding Domain”. Hacettepe Journal of Biology and Chemistry, vol. 49, no. 4, 2021, pp. 367-74, doi:10.15671/hjbc.776430.
Vancouver	Biterge Süt B. Structural analysis of novel amino acid substitutions in SARS-CoV-2 spike protein receptor-binding domain. HJBC. 2021;49(4):367-74.

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