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Basic Characteristics of Mutations
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Mutation Site
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T478K |
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Mutation Site Sentence
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Finally, we identify sets of comutations that have a high likelihood of massive growth: [A411S, L452R, T478K], [L452R, T478K, N501Y], [V401L, L452R, T478K], [K417N, L452R, T478K], [L452R, T478K, E484K, N501Y], and [P384L, K417N, E484K, N501Y]. |
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Mutation Level
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Amino acid level |
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Mutation Type
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Nonsynonymous substitution |
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Gene/Protein/Region
|
S |
|
Standardized Encoding Gene
|
S
|
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Genotype/Subtype
|
- |
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Viral Reference
|
-
|
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Functional Impact and Mechanisms
|
|
Disease
|
COVID-19
|
|
Immune
|
Y |
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Target Gene
|
-
|
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Clinical and Epidemiological Correlations
|
|
Clinical Information
|
- |
|
Treatment
|
- |
|
Location
|
- |
|
Literature Information
|
|
PMID
|
35133792
|
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Title
|
Emerging Vaccine-Breakthrough SARS-CoV-2 Variants
|
|
Author
|
Wang R,Chen J,Hozumi Y,Yin C,Wei GW
|
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Journal
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ACS infectious diseases
|
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Journal Info
|
2022 Mar 11;8(3):546-556
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Abstract
|
The surge of COVID-19 infections has been fueled by new SARS-CoV-2 variants, namely Alpha, Beta, Gamma, Delta, and so forth. The molecular mechanism underlying such surge is elusive due to the existence of 28,554 unique mutations, including 4,653 non-degenerate mutations on the spike protein. Understanding the molecular mechanism of SARS-CoV-2 transmission and evolution is a prerequisite to foresee the trend of emerging vaccine-breakthrough variants and the design of mutation-proof vaccines and monoclonal antibodies. We integrate the genotyping of 1,489,884 SARS-CoV-2 genomes, a library of 130 human antibodies, tens of thousands of mutational data, topological data analysis, and deep learning to reveal SARS-CoV-2 evolution mechanism and forecast emerging vaccine-breakthrough variants. We show that prevailing variants can be quantitatively explained by infectivity-strengthening and vaccine-escape (co-)mutations on the spike protein RBD due to natural selection and/or vaccination-induced evolutionary pressure. We illustrate that infectivity strengthening mutations were the main mechanism for viral evolution, while vaccine-escape mutations become a dominating viral evolutionary mechanism among highly vaccinated populations. We demonstrate that Lambda is as infectious as Delta but is more vaccine-resistant. We analyze emerging vaccine-breakthrough comutations in highly vaccinated countries, including the United Kingdom, the United States, Denmark, and so forth. Finally, we identify sets of comutations that have a high likelihood of massive growth: [A411S, L452R, T478K], [L452R, T478K, N501Y], [V401L, L452R, T478K], [K417N, L452R, T478K], [L452R, T478K, E484K, N501Y], and [P384L, K417N, E484K, N501Y]. We predict they can escape existing vaccines. We foresee an urgent need to develop new virus combating strategies.
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Sequence Data
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-
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|
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