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Vaccine-escape and fast-growing mutations in the United Kingdom, the United States, Singapore, Spain, India, and other COVID-19-devastated countries.
Genomics. 2021 07; 113(4):2158-2170.G

Abstract

Recently, the SARS-CoV-2 variants from the United Kingdom (UK), South Africa, and Brazil have received much attention for their increased infectivity, potentially high virulence, and possible threats to existing vaccines and antibody therapies. The question remains if there are other more infectious variants transmitted around the world. We carry out a large-scale study of 506,768 SARS-CoV-2 genome isolates from patients to identify many other rapidly growing mutations on the spike (S) protein receptor-binding domain (RBD). We reveal that essentially all 100 most observed mutations strengthen the binding between the RBD and the host angiotensin-converting enzyme 2 (ACE2), indicating the virus evolves toward more infectious variants. In particular, we discover new fast-growing RBD mutations N439K, S477N, S477R, and N501T that also enhance the RBD and ACE2 binding. We further unveil that mutation N501Y involved in United Kingdom (UK), South Africa, and Brazil variants may moderately weaken the binding between the RBD and many known antibodies, while mutations E484K and K417N found in South Africa and Brazilian variants, L452R and E484Q found in India variants, can potentially disrupt the binding between the RBD and many known antibodies. Among these RBD mutations, L452R is also now known as part of the California variant B.1.427. Finally, we hypothesize that RBD mutations that can simultaneously make SARS-CoV-2 more infectious and disrupt the existing antibodies, called vaccine escape mutations, will pose an imminent threat to the current crop of vaccines. A list of most likely vaccine escape mutations is given, including S494P, Q493L, K417N, F490S, F486L, R403K, E484K, L452R, K417T, F490L, E484Q, and A475S. Mutation T478K appears to make the Mexico variant B.1.1.222 the most infectious one. Our comprehensive genetic analysis and protein-protein binding study show that the genetic evolution of SARS-CoV-2 on the RBD, which may be regulated by host gene editing, viral proofreading, random genetic drift, and natural selection, gives rise to more infectious variants that will potentially compromise existing vaccines and antibody therapies.

Authors+Show Affiliations

Department of Mathematics, Michigan State University, MI 48824, USA.Department of Mathematics, Michigan State University, MI 48824, USA.Department of Mathematics, Michigan State University, MI 48824, USA.Department of Mathematics, Michigan State University, MI 48824, USA; Department of Electrical and Computer Engineering, Michigan State University, MI 48824, USA; Department of Biochemistry and Molecular Biology, Michigan State University, MI 48824, USA. Electronic address: weig@msu.edu.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

34004284

Citation

Wang, Rui, et al. "Vaccine-escape and Fast-growing Mutations in the United Kingdom, the United States, Singapore, Spain, India, and Other COVID-19-devastated Countries." Genomics, vol. 113, no. 4, 2021, pp. 2158-2170.
Wang R, Chen J, Gao K, et al. Vaccine-escape and fast-growing mutations in the United Kingdom, the United States, Singapore, Spain, India, and other COVID-19-devastated countries. Genomics. 2021;113(4):2158-2170.
Wang, R., Chen, J., Gao, K., & Wei, G. W. (2021). Vaccine-escape and fast-growing mutations in the United Kingdom, the United States, Singapore, Spain, India, and other COVID-19-devastated countries. Genomics, 113(4), 2158-2170. https://doi.org/10.1016/j.ygeno.2021.05.006
Wang R, et al. Vaccine-escape and Fast-growing Mutations in the United Kingdom, the United States, Singapore, Spain, India, and Other COVID-19-devastated Countries. Genomics. 2021;113(4):2158-2170. PubMed PMID: 34004284.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Vaccine-escape and fast-growing mutations in the United Kingdom, the United States, Singapore, Spain, India, and other COVID-19-devastated countries. AU - Wang,Rui, AU - Chen,Jiahui, AU - Gao,Kaifu, AU - Wei,Guo-Wei, Y1 - 2021/05/15/ PY - 2021/04/01/received PY - 2021/04/30/revised PY - 2021/05/10/accepted PY - 2021/5/19/pubmed PY - 2021/7/15/medline PY - 2021/5/18/entrez KW - Antibody KW - Binding affinity KW - COVID-19 KW - Deep learning KW - Mutation KW - Persistent homology KW - SARS-CoV-2 KW - Vaccine escape SP - 2158 EP - 2170 JF - Genomics JO - Genomics VL - 113 IS - 4 N2 - Recently, the SARS-CoV-2 variants from the United Kingdom (UK), South Africa, and Brazil have received much attention for their increased infectivity, potentially high virulence, and possible threats to existing vaccines and antibody therapies. The question remains if there are other more infectious variants transmitted around the world. We carry out a large-scale study of 506,768 SARS-CoV-2 genome isolates from patients to identify many other rapidly growing mutations on the spike (S) protein receptor-binding domain (RBD). We reveal that essentially all 100 most observed mutations strengthen the binding between the RBD and the host angiotensin-converting enzyme 2 (ACE2), indicating the virus evolves toward more infectious variants. In particular, we discover new fast-growing RBD mutations N439K, S477N, S477R, and N501T that also enhance the RBD and ACE2 binding. We further unveil that mutation N501Y involved in United Kingdom (UK), South Africa, and Brazil variants may moderately weaken the binding between the RBD and many known antibodies, while mutations E484K and K417N found in South Africa and Brazilian variants, L452R and E484Q found in India variants, can potentially disrupt the binding between the RBD and many known antibodies. Among these RBD mutations, L452R is also now known as part of the California variant B.1.427. Finally, we hypothesize that RBD mutations that can simultaneously make SARS-CoV-2 more infectious and disrupt the existing antibodies, called vaccine escape mutations, will pose an imminent threat to the current crop of vaccines. A list of most likely vaccine escape mutations is given, including S494P, Q493L, K417N, F490S, F486L, R403K, E484K, L452R, K417T, F490L, E484Q, and A475S. Mutation T478K appears to make the Mexico variant B.1.1.222 the most infectious one. Our comprehensive genetic analysis and protein-protein binding study show that the genetic evolution of SARS-CoV-2 on the RBD, which may be regulated by host gene editing, viral proofreading, random genetic drift, and natural selection, gives rise to more infectious variants that will potentially compromise existing vaccines and antibody therapies. SN - 1089-8646 UR - https://www.unboundmedicine.com/medline/citation/34004284/Vaccine_escape_and_fast_growing_mutations_in_the_United_Kingdom_the_United_States_Singapore_Spain_India_and_other_COVID_19_devastated_countries_ DB - PRIME DP - Unbound Medicine ER -