The Increased Amyloidogenicity of Spike RBD and pH-Dependent Binding to ACE2 May Contribute to the Transmissibility and Pathogenic Properties of SARS-CoV-2 Omicron as Suggested by In Silico Study
Abstract
:1. Introduction
2. Results
2.1. Omicron RBD Better Binds to ACE2 in Protonated form When Compared to Delta by MD Simulations
2.2. Amyloidogenic Properties of Spike RBDs of SARS-CoV-2 Variants
3. Discussion
4. Materials and Methods
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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SARS-CoV-2 Variant | RBD | RBM | Transmissibility (Average R0 Increase) | ||||
---|---|---|---|---|---|---|---|
RBD | pI | Charge at pH 7 | RBM | pI | Charge at pH 7 | ||
Wuhan-Hu-1 (WT) | 323–531 | 8.27 | 3.9 | 438–506 | 7.94 | 0.8 | 1 |
Alpha | 320–528 | 8.27 | 3.9 | 435–503 | 7.94 | 0.8 | ~29% increased over WT [69] |
Beta | 320–528 | 8.42 | 4.9 | 435–503 | 8.83 | 2.8 | ~25% increased over WT [69] |
Epsilon | 323–531 | 8.42 | 4.9 | 438–506 | 8.45 | 1.9 | 18.6–24% increased over WT [70] |
Gamma | 323–531 | 8.42 | 4.9 | 438–506 | 8.83 | 2.8 | ~38% increased over WT [69] |
Delta | 321–529 | 8.57 | 5.9 | 436–504 | 8.85 | 2.8 | ~97% increased over WT [69] |
Omicron BA.1 | 320–528 | 8.70 | 7.2 | 435–503 | 9.55 | 6.1 | ~3.2 times more than Delta [71,72] |
Omicron BA.2 | 320–528 | 8.70 | 7.2 | 435–503 | 9.55 | 6.1 | ~1.4 times more than BA.1 [72] |
RBD | Amyloidogenicity * (%) |
---|---|
SARS_CoV (310–517) | 26.9% |
Delta (321–529) | 29.7% |
Epsilon (323–531) | 29.7% |
Wuhan-Hu-1 (323–531) | 34.4% |
Alpha (320–528) | 34.4% |
Beta (320–528) | 34.4% |
Gamma (323–521) | 34.4% |
Omicron BA.1 (320–528) | 38.3% |
Omicron BA.2 (320–528) | 40.7% |
HCoV-NL63 (481–616) ** | 47.1% |
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Aksenova, A.Y.; Likhachev, I.V.; Grishin, S.Y.; Galzitskaya, O.V. The Increased Amyloidogenicity of Spike RBD and pH-Dependent Binding to ACE2 May Contribute to the Transmissibility and Pathogenic Properties of SARS-CoV-2 Omicron as Suggested by In Silico Study. Int. J. Mol. Sci. 2022, 23, 13502. https://doi.org/10.3390/ijms232113502
Aksenova AY, Likhachev IV, Grishin SY, Galzitskaya OV. The Increased Amyloidogenicity of Spike RBD and pH-Dependent Binding to ACE2 May Contribute to the Transmissibility and Pathogenic Properties of SARS-CoV-2 Omicron as Suggested by In Silico Study. International Journal of Molecular Sciences. 2022; 23(21):13502. https://doi.org/10.3390/ijms232113502
Chicago/Turabian StyleAksenova, Anna Y., Ilya V. Likhachev, Sergei Y. Grishin, and Oxana V. Galzitskaya. 2022. "The Increased Amyloidogenicity of Spike RBD and pH-Dependent Binding to ACE2 May Contribute to the Transmissibility and Pathogenic Properties of SARS-CoV-2 Omicron as Suggested by In Silico Study" International Journal of Molecular Sciences 23, no. 21: 13502. https://doi.org/10.3390/ijms232113502