scholarly journals Epidemiological Model Suggests D614G Spike Protein Mutation Accelerates Transmission of COVID-19 — Worldwide, 2020

2020 ◽  
Vol 2 (49) ◽  
pp. 946-947
Author(s):  
Liang Wang ◽  
◽  
Yuhai Bi ◽  
George F. Gao ◽  
Keyword(s):  
Epidemiological Model ◽  
Spike Protein ◽  
Protein Mutation

scholarly journals Transmission, infectivity, and antibody neutralization of an emerging SARS-CoV-2 variant in California carrying a L452R spike protein mutation

2021 ◽  
Author(s):  
Xianding Deng ◽  
Miguel A Garcia-Knight ◽  
Mir M. Khalid ◽  
Venice Servellita ◽  
Candace Wang ◽  
...  
Keyword(s):  
Genome Sequencing ◽  
Cell Cultures ◽  
Spike Protein ◽  
Nasopharyngeal Swab ◽  
Whole Genome ◽  
Wild Type ◽  
Antibody Neutralization ◽  
Protein Mutation ◽  
Viral Shedding

AbstractWe identified a novel SARS-CoV-2 variant by viral whole-genome sequencing of 2,172 nasal/nasopharyngeal swab samples from 44 counties in California. Named B.1.427/B.1.429 to denote its 2 lineages, the variant emerged around May 2020 and increased from 0% to >50% of sequenced cases from September 1, 2020 to January 29, 2021, exhibiting an 18.6-24% increase in transmissibility relative to wild-type circulating strains. The variant carries 3 mutations in the spike protein, including an L452R substitution. Our analyses revealed 2-fold increased B.1.427/B.1.429 viral shedding in vivo and increased L452R pseudovirus infection of cell cultures and lung organoids, albeit decreased relative to pseudoviruses carrying the N501Y mutation found in the B.1.1.7, B.1.351, and P.1 variants. Antibody neutralization assays showed 4.0 to 6.7-fold and 2.0-fold decreases in neutralizing titers from convalescent patients and vaccine recipients, respectively. The increased prevalence of a more transmissible variant in California associated with decreased antibody neutralization warrants further investigation.

scholarly journals Abundant transmission of Corona Virus Nsp2 RNA Topoisomerse I120F Mutants with Concurrence D614G Spike Protein Mutation in Australia

2021 ◽  
Author(s):  
ASIT KUMAR CHAKRABORTY
Keyword(s):  
Amino Acid ◽  
Topoisomerase I ◽  
Sequence Similarity ◽  
Virus Transmission ◽  
Spike Protein ◽  
Virus Protein ◽  
Dna Topoisomerase ◽  
Amino Acid Homology ◽  
Protein Mutation ◽  
Corona Virus

We previously predicted Nsp2 Corona virus protein as RNA topoisomerase through amino acid homology among Vibrio haemolytica DNA topoisomerase IA/IV as well as DNA primase, DNA gyrase and bi-subunit Trypanosoma brucei DNA topoisomerase IB. Many DNA topoisomerase I/III have RNA topoisomerase activity and such ubiquitous enzymes are conserved and involved in the regulation of replication and transcription. We have checked here mutational profile of Nsp2 RNA topoisomerase analyzing >10000 orf1a 4405 amino acid length Corona virus polyprotein. Mutant proteins were selected by BLAST search having 99.84% sequence similarity and 181-818aa portion Nsp2 protein (protein id. QIU82057) was analyzed using CLUSTAL Omega software. We found 26 different mutations where most changes were selected at Isoleucine and Alanine into Valine or Leucine into Phenylanaline pinpointing conserved nature of the Corona virus RNA topoisomerase. Major nonsense very abundant mutations were found at I120F (Isoleucine to Phenylalanine). Other important mutations were R27C, I198V, T85I, L410F, I559V and P583S. The I120F mutation was abundant in Australian isolates and its spread was seen in the Bangladesh and other countries like USA. We suggest that abundant I120F mutation of Nsp2 Topoisomerase may increase transmission of Corona virus by stabilizing RNA structure for efficient virus pakaging. Interestingly, such mutations were found in association of D614G mutation of Spike protein, known to >70% increase infectivity. On the contrary, all P583S Nsp2 mutants analyzed had no concurrence D614G spike protein mutation. Many silent mutations (5-7) were detected by genome wide analysis but no N501Y Spike protein mutation. This is first report that predicts a link of greater Corona virus transmission with Nsp2 protein I120F and spike protein D614G mutations.

scholarly journals N‐terminal domain of SARS CoV‐2 spike protein mutation associated reduction in effectivity of neutralizing antibody with vaccinated individuals

2021 ◽  
Author(s):  
Yogendar Singh ◽  
Neeraj Kumar Fuloria ◽  
Shivkanya Fuloria ◽  
Vetriselvan Subramaniyan ◽  
Dhanalekshmi Unnikrishnan Meenakshi ◽  
...  
Keyword(s):  
Neutralizing Antibody ◽  
Spike Protein ◽  
Protein Mutation ◽  
Terminal Domain

scholarly journals Recombination and low-diversity confound homoplasy-based methods to detect the effect of SARS-CoV-2 mutations on viral transmissibility

2021 ◽  
Author(s):  
Elena E. Giorgi ◽  
Tanmoy Bhattacharya ◽  
Will Fischer ◽  
Hyejin Yoon ◽  
Werner Abfalterer ◽  
...  
Keyword(s):  
Animal Models ◽  
Spike Protein ◽  
Dominant Form ◽  
Protein Mutation ◽  
Low Diversity

AbstractThe SARS-CoV-2 variant carrying the Spike protein mutation G614 was first detected in late January 2020 and within a few months became the dominant form globally. In the months that followed, many studies, both in vitro and in animal models, showed that variants carrying this mutation were more infectious and more readily transmitted than the ancestral Wuhan form. Here we investigate why a recently published study by van Dorp et al. failed to detect such higher transmissibility of the G614 variant using homoplasy-based methods. We show that both low diversity and recombination confound the methods utilized by van Dorp et al. and significantly decrease their sensitivity. Furthermore, though they claim no evidence of recombination in their dataset, we and several other studies identify a subset of the sequences as recombinants, possibly enough to affect their statistic adversely.

scholarly journals Evolutionary and structural analyses of SARS-CoV-2 D614G spike protein mutation now documented worldwide

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Sandra Isabel ◽  
Lucía Graña-Miraglia ◽  
Jahir M. Gutierrez ◽  
Cedoljub Bundalovic-Torma ◽  
Helen E. Groves ◽  
...  
Keyword(s):  
Spike Protein ◽  
Protein Mutation

scholarly journals Association of E484K spike protein mutation with SARS-CoV-2 infection in vaccinated persons---Maryland, January – May 2021

2021 ◽  
Author(s):  
Kenneth A Feder ◽  
Ami Patel ◽  
Venkata R Vepachedu ◽  
Catherine Dominguez ◽  
Eric N Keller ◽  
...  
Keyword(s):  
Spike Protein ◽  
Protein Mutation ◽  
Adjusted Analysis

Abstract Among 9,048 people infected with SARS-CoV-2 between January-May, 2021 in Maryland, in regression-adjusted analysis, SARS-CoV-2 viruses carrying the spike protein mutation E484K were disproportionately prevalent among persons infected after full vaccination against COVID-19 as compared to infected persons who were not fully vaccinated (aOR 1.96, 95% CI, 1.36 to 2.83).

scholarly journals Inferring effects of mutations on SARS-CoV-2 transmission from genomic surveillance data

2022 ◽  
Author(s):  
Brian Lee ◽  
Muhammad Saqib Sohail ◽  
Elizabeth Finney ◽  
Syed Faraz Ahmed ◽  
Ahmed Abdul Quadeer ◽  
...  
Keyword(s):  
Transmission Rate ◽  
Rapid Identification ◽  
Epidemiological Model ◽  
Surveillance Data ◽  
Spike Protein ◽  
Regional Data ◽  
Outbreak Control

New and more transmissible variants of SARS-CoV-2 have arisen multiple times over the course of the pandemic. Rapidly identifying mutations that affect transmission could facilitate outbreak control efforts and highlight new variants that warrant further study. Here we develop an analytical epidemiological model that infers the transmission effects of mutations from genomic surveillance data. Applying our model to SARS-CoV-2 data across many regions, we find multiple mutations that strongly affect the transmission rate, both within and outside the Spike protein. We also quantify the effects of travel and competition between different lineages on the inferred transmission effects of mutations. Importantly, our model detects lineages with increased transmission as they arise. We infer significant transmission advantages for the Alpha and Delta variants within a week of their appearances in regional data, when their regional frequencies were only around 1%. Our model thus enables the rapid identification of variants and mutations that affect transmission from genomic surveillance data.

scholarly journals A Discernable Increase in the Severe Acute Respiratory Syndrome Coronavirus 2 R.1 Lineage Carrying an E484K Spike Protein Mutation in Japan

2021 ◽  
Author(s):  
Tsuyoshi Sekizuka ◽  
Kentaro Itokawa ◽  
Masanori Hashino ◽  
Kazuhiro Okubo ◽  
Asami Ohnishi ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Spike Protein ◽  
Protein Mutation

Three COVID-19 waves in Japan have been characterized by the presence of distinct PANGO lineages (B.1.1. 162, B.1.1.284, and B.1.1.214). Recently, in addition to the B.1.1.7 lineage, which shows 25% abundance, an R.1 lineage carrying the E484K mutation in the spike protein was found to show up to 40% predominance.

scholarly journals Spike mutation D614G alters SARS-CoV-2 fitness and neutralization susceptibility

2020 ◽  
Author(s):  
Jessica A. Plante ◽  
Yang Liu ◽  
Jianying Liu ◽  
Hongjie Xia ◽  
Bryan A. Johnson ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Viral Replication ◽  
Vaccine Efficacy ◽  
Human Lung ◽  
Lung Epithelial Cells ◽  
Spike Protein ◽  
Protein Mutation ◽  
Viral Spread ◽  
Lung Epithelial ◽  
Human Lung Epithelial Cells

AbstractA spike protein mutation D614G became dominant in SARS-CoV-2 during the COVID-19 pandemic. However, the mutational impact on viral spread and vaccine efficacy remains to be defined. Here we engineer the D614G mutation in the SARS-CoV-2 USA-WA1/2020 strain and characterize its effect on viral replication, pathogenesis, and antibody neutralization. The D614G mutation significantly enhances SARS-CoV-2 replication on human lung epithelial cells and primary human airway tissues, through an improved infectivity of virions with the spike receptor-binding domain in an “up” conformation for binding to ACE2 receptor. Hamsters infected with D614 or G614 variants developed similar levels of weight loss. However, the G614 virus produced higher infectious titers in the nasal washes and trachea, but not lungs, than the D614 virus. The hamster results confirm clinical evidence that the D614G mutation enhances viral loads in the upper respiratory tract of COVID-19 patients and may increases transmission. For antibody neutralization, sera from D614 virus-infected hamsters consistently exhibit higher neutralization titers against G614 virus than those against D614 virus, indicating that (i) the mutation may not reduce the ability of vaccines in clinical trials to protect against COVID-19 and (ii) therapeutic antibodies should be tested against the circulating G614 virus before clinical development.ImportanceUnderstanding the evolution of SARS-CoV-2 during the COVID-19 pandemic is essential for disease control and prevention. A spike protein mutation D614G emerged and became dominant soon after the pandemic started. By engineering the D614G mutation into an authentic wild-type SARS-CoV-2 strain, we demonstrate the importance of this mutation to (i) enhanced viral replication on human lung epithelial cells and primary human airway tissues, (ii) improved viral fitness in the upper airway of infected hamsters, and (iii) increased susceptibility to neutralization. Together with clinical findings, our work underscores the importance of this mutation in viral spread, vaccine efficacy, and antibody therapy.

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