Dataset Information

Novel Highly Divergent SARS-CoV-2 Lineage With the Spike Substitutions L249S and E484K.

ABSTRACT: COVID-19 pandemics has led to genetic diversification of SARS-CoV-2 and the appearance of variants with potential impact in transmissibility and viral escape from acquired immunity. We report a new and highly divergent lineage containing 21 distinctive mutations (10 non-synonymous, eight synonymous, and three substitutions in non-coding regions). The amino acid changes L249S and E484K located at the CTD and RBD of the Spike protein could be of special interest due to their potential biological role in the virus-host relationship. Further studies are required for monitoring the epidemiologic impact of this new lineage.

SUBMITTER: Laiton-Donato K

PROVIDER: S-EPMC8273171 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Novel Highly Divergent SARS-CoV-2 Lineage With the Spike Substitutions L249S and E484K.

Laiton-Donato Katherine K Usme-Ciro Jose A JA Franco-Muñoz Carlos C Álvarez-Díaz Diego A DA Ruiz-Moreno Hector Alejandro HA Reales-González Jhonnatan J Prada Diego Andrés DA Corchuelo Sheryll S Herrera-Sepúlveda Maria T MT Naizaque Julian J Santamaría Gerardo G Wiesner Magdalena M Walteros Diana Marcela DM Ospina Martínez Martha Lucia ML Mercado-Reyes Marcela M

Frontiers in medicine 20210628

COVID-19 pandemics has led to genetic diversification of SARS-CoV-2 and the appearance of variants with potential impact in transmissibility and viral escape from acquired immunity. We report a new and highly divergent lineage containing 21 distinctive mutations (10 non-synonymous, eight synonymous, and three substitutions in non-coding regions). The amino acid changes L249S and E484K located at the CTD and RBD of the Spike protein could be of special interest due to their potential biological r ...[more]

PMID: 34262921

Similar Datasets

Project description:BackgroundAn ideal animal model to study SARS-coronavirus 2 (SARS-CoV-2) pathogenesis and evaluate therapies and vaccines should reproduce SARS-CoV-2 infection and recapitulate lung disease like those seen in humans. The angiotensin-converting enzyme 2 (ACE2) is a functional receptor for SARS-CoV-2, but mice are resistant to the infection because their ACE2 is incompatible with the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein .MethodsSARS-CoV-2 was passaged in BALB/c mice to obtain mouse-adapted virus strain. Complete genome deep sequencing of different generations of viruses was performed to characterize the dynamics of the adaptive mutations in SARS-CoV-2. Indirect immunofluorescence analysis and Biolayer interferometry experiments determined the binding affinity of mouse-adapted SARS-CoV-2 WBP-1 RBD to mouse ACE2 and human ACE2. Finally, we tested whether TLR7/8 agonist Resiquimod (R848) could also inhibit the replication of WBP-1 in the mouse model.FindingsThe mouse-adapted strain WBP-1 showed increased infectivity in BALB/c mice and led to severe interstitial pneumonia. We characterized the dynamics of the adaptive mutations in SARS-CoV-2 and demonstrated that Q493K and Q498H in RBD significantly increased its binding affinity towards mouse ACE2. Additionally, the study tentatively found that the TLR7/8 agonist Resiquimod was able to protect mice against WBP-1 challenge. Therefore, this mouse-adapted strain is a useful tool to investigate COVID-19 and develop new therapies.InterpretationWe found for the first time that the Q493K and Q498H mutations in the RBD of WBP-1 enhanced its interactive affinities with mACE2. The mouse-adapted SARS-CoV-2 provides a valuable tool for the evaluation of novel antiviral and vaccine strategies. This study also tentatively verified the antiviral activity of TLR7/8 agonist Resiquimod against SARS-CoV-2 in vitro and in vivo.FundingThis research was funded by the National Key Research and Development Program of China (2020YFC0845600) and Emergency Science and Technology Project of Hubei Province (2020FCA046) and Robert A. Welch Foundation (C-1565).

Dataset Information

Novel Highly Divergent SARS-CoV-2 Lineage With the Spike Substitutions L249S and E484K.

Publications

Novel Highly Divergent SARS-CoV-2 Lineage With the Spike Substitutions L249S and E484K.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets