microbial gwas studies revealing combinations of omicron rbd mutations existed and CORD-Papers-2022-06-02 (Version 1)

Title: Microbial GWAS studies revealing combinations of Omicron RBD mutations existed and may contribute to antibody evasion and ACE2 binding
Abstract: Since Omicron variant of SARS-CoV-2 was first detected in South Africa (SA) it has now dominated in United Kingdom (UK) of Europe and United State (USA) of North America. A prominent feature of this variant is the gathering of spike protein mutations in particularly at the receptor binding domain (RBD). These RBD mutations essentially contribute to antibody resistance of current immune approaches. During global spillover combinations of RBD mutations may exist and synergistically contribute to antibody resistance in fact. Using three geographic-stratified genome wide association studies (GWAS) we observed that RBD combinations exhibited a geographic pattern and genetical associated such as five common mutations in both UK and USA Omicron six or two specific mutations in UK or USA Omicron. Although the UK specific RBD mutations can be further classified into two separated sub-groups of combination based on linkage disequilibrium analysis. Functional analysis indicated that the common RBD combinations (fold change -11.59) alongside UK or USA specific mutations significantly reduced neutralization (fold change -38.72 -18.11). As RBD overlaps with angiotensin converting enzyme 2(ACE2) binding motif protein-protein contact analysis indicated that the common RBD mutations enhanced ACE2 binding accessibility and were further strengthened by UK or USA-specific RBD mutations. Spatiotemporal evolution analysis indicated that UK-specific RBD mutations largely contribute to global spillover. Collectively we have provided genetic evidence of RBD combinations and estimated their effects on antibody evasion and ACE2 binding accessibility.
Published: 2022-01-21
DOI: 10.1101/2022.01.19.22269510
DOI_URL: http://doi.org/10.1101/2022.01.19.22269510
Author Name: Ou X
Author link: https://covid19-data.nist.gov/pid/rest/local/author/ou_x
Author Name: Yang Z
Author link: https://covid19-data.nist.gov/pid/rest/local/author/yang_z
Author Name: Zhu D
Author link: https://covid19-data.nist.gov/pid/rest/local/author/zhu_d
Author Name: Mao S
Author link: https://covid19-data.nist.gov/pid/rest/local/author/mao_s
Author Name: Wang M
Author link: https://covid19-data.nist.gov/pid/rest/local/author/wang_m
Author Name: Jia R
Author link: https://covid19-data.nist.gov/pid/rest/local/author/jia_r
Author Name: Chen S
Author link: https://covid19-data.nist.gov/pid/rest/local/author/chen_s
Author Name: Liu M
Author link: https://covid19-data.nist.gov/pid/rest/local/author/liu_m
Author Name: Yang Q
Author link: https://covid19-data.nist.gov/pid/rest/local/author/yang_q
Author Name: Wu Y
Author link: https://covid19-data.nist.gov/pid/rest/local/author/wu_y
Author Name: Zhao X
Author link: https://covid19-data.nist.gov/pid/rest/local/author/zhao_x
Author Name: Zhang S
Author link: https://covid19-data.nist.gov/pid/rest/local/author/zhang_s
Author Name: Huang J
Author link: https://covid19-data.nist.gov/pid/rest/local/author/huang_j
Author Name: Gao Q
Author link: https://covid19-data.nist.gov/pid/rest/local/author/gao_q
Author Name: Liu Y
Author link: https://covid19-data.nist.gov/pid/rest/local/author/liu_y
Author Name: Zhang L
Author link: https://covid19-data.nist.gov/pid/rest/local/author/zhang_l
Author Name: Peppelenbosch M
Author link: https://covid19-data.nist.gov/pid/rest/local/author/peppelenbosch_m
Author Name: Pan Q
Author link: https://covid19-data.nist.gov/pid/rest/local/author/pan_q
Author Name: Cheng A c
Author link: https://covid19-data.nist.gov/pid/rest/local/author/cheng_a_c
license: medrxiv
source_x: MedRxiv
url: http://medrxiv.org/cgi/content/short/2022.01.19.22269510v1?rss=1
has_full_text: FALSE
G_ID: microbial_gwas_studies_revealing_combinations_of_omicron_rbd_mutations_existed_and