Transmission, infectivity, and neutralization of a spike L452R SARS-CoV-2 variant

Deng, Xianding; Garcia-Knight, Miguel; Khalid, Mir M.; Servellita, Venice; Wang, Candace; Morris, Mary Kate; Sotomayor-González, Alicia; Glasner, Dustin R.; Reyes, Kevin; Gliwa, Amelia; Reddy, Nikitha P.; Martín, Claudia Sánchez San; Federman, Scot; Cheng, Jing; Balcerek, Joanna; Taylor, Jordan E.; Streithorst, Jessica; Miller, Steve; Sreekumar, Bharath; Chen, Peiyi; Schulze‐Gahmen, Ursula; Taha, Taha Y.; Hayashi, Jennifer M.; Simoneau, Camille R.; Kumar, G. Renuka; McMahon, Sarah; Lidsky, Peter V.; Xiao, Yinghong; Hemarajata, Peera; Green, Nicole M.; Espinosa, Alex; Kath, Chantha; Haw, Monica; Bell, John; Hacker, Jill K.; Hanson, Carl V.; Wadford, Debra A.; Anaya, Carlos; Ferguson, Donna; Frankino, Phillip A.; Shivram, Haridha; Lareau, Liana F.; Wyman, Stacia K.; Ott, Mélanie; Andino, Raul; Chiu, Charles Y.

doi:10.1016/j.cell.2021.04.025

Cited by 488 publications

(391 citation statements)

References 65 publications

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“…Of the 63 publications included, five were non-peer reviewed preprints [16,17,52,54,66]. Eleven articles reported in vitro, in silico or animal model studies [15,18,19,[22][23][24][25][26][27][28][29]; nineteen articles reported clinical studies [16,[37][38][39][41][42][43][44][45][46][47][48][49]51,[70][71][72][73]. The remaining 33 articles analyzed SARS-CoV-2 genomes downloaded from the GISAID or other available databases with patient status [8][9][10][11]20,21,[30][31][32][33][34][35][36]40,50,…”

Section: Study Selection and Types Of Studiesmentioning

confidence: 99%

“…Twenty-five studies reported the relation between viral mutations and virus load or infectivity of SARS-CoV-2 (Table 2), of which five articles (two in vitro/animal model studies [18,19], two studies based on SARS-CoV-2 genomes downloaded from electronic databases or community-based testing datasets (bigdata analysis) [20,21] and one clinical study [16]) showed no impact of mutations with infectivity of SARS-CoV-2. The remaining 20 studies (nine in vitro/animal model or in silico studies [15,[22][23][24][25][26][27][28][29], eight bigdata analyses [9,[30][31][32][33][34][35][36] and three clinical studies [37][38][39]) showed that SARS-CoV-2 variants were significantly associated with increase in infectivity. All studies performed on the variants of concern (VOCs) have linked these mutations to increased viral transmissibility [23,[27][28][29][34][35][36]38,39], except for one study by Li et al [19].…”

Section: Relation Between Viral Mutation and Infectivity Of Sars-cov-2mentioning

confidence: 99%

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SARS-CoV-2 Infectivity and Severity of COVID-19 According to SARS-CoV-2 Variants: Current Evidence

Dao

Hoang

Colson

et al. 2021

JCM

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Background: We conducted this review to summarize the relation between viral mutation and infectivity of SARS-CoV-2 and also the severity of COVID-19 in vivo and in vitro. Method: Articles were identified through a literature search until 31 May 2021, in PubMed, Web of Science and Google Scholar. Results: Sixty-three studies were included. To date, most studies showed that the viral mutations, especially the D614G variant, correlate with a higher infectivity than the wild-type virus. However, the evidence of the association between viral mutation and severity of the disease is scant. A SARS-CoV-2 variant with a 382-nucleotide deletion was associated with less severe infection in patients. The 11,083G > U mutation was significantly associated with asymptomatic patients. By contrast, ORF1ab 4715L and S protein 614G variants were significantly more frequent in patients from countries where high fatality rates were also reported. The current evidence showed that variants of concern have led to increased infectivity and deteriorating epidemiological situations. However, the relation between this variant and severity of COVID-19 infection was contradictory. Conclusion: The COVID-19 pandemic continues to spread worldwide. It is necessary to anticipate large clinical cohorts to evaluate the virulence and transmissibility of SARS-CoV-2 mutants.

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Section: Study Selection and Types Of Studiesmentioning

confidence: 99%

Section: Relation Between Viral Mutation and Infectivity Of Sars-cov-2mentioning

confidence: 99%

SARS-CoV-2 Infectivity and Severity of COVID-19 According to SARS-CoV-2 Variants: Current Evidence

Dao

Hoang

Colson

et al. 2021

JCM

View full text Add to dashboard Cite

show abstract

“…We also identified seven patients with COVID-19 caused by B.1.617.1 or B.1.617.2, variants reported to be causing widespread disease and extensive public health concern in India. [43][44][45][46][47][48] In the aggregate, our genome data show that VOC and VOI now account for the great majority of all new COVID-19 cases in our region.…”

Section: [Introduction]mentioning

confidence: 65%

Trajectory of Growth of SARS-CoV-2 Variants in Houston, Texas, January through May 2021 Based on 12,476 Genome Sequences

Olsen

Christensen

Long

et al. 2021

Preprint

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Genetic variants of the SARS-CoV-2 virus are of substantial concern because they can detrimentally alter the trajectory of the ongoing pandemic, and disease course in individual patients. Here we report genome sequences from 11,568 COVID-19 patients in the Houston Methodist healthcare system dispersed throughout the metroplex that were diagnosed from January 1, 2021 through April 30, 2021. This sample represents 94% of Houston Methodist cases and 4.6% of all reported cases in the metropolitan area during this period. The SARS-CoV-2 variant designated UK B.1.1.7 increased very rapidly, and now causes 75%-90% of all new cases in the Houston area. Five of the 2,543 B.1.1.7 genomes had an E484K change in spike protein. Compared with non-B.1.1.7 patients, individuals infected with B.1.1.7 had a significantly lower cycle threshold value (considered to be a proxy for higher virus load) and higher rate of hospitalization. Other variants (e.g., B.1.429, B.1.427, P.1, P.2, and R.1) also increased rapidly in frequency, although the magnitude was less than for B.1.1.7. We also identified 42 patients with a recently described R.1 variant that has an E484K amino acid replacement, and seven patients with the B.1.617 "India" variants. In the aggregate, our study shows the occurrence of a diverse array of concerning SARS-CoV-2 variants circulating in a major metropolitan area, documents B.1.1.7 as the major cause of new cases in Houston and heralds the arrival and spread of B.1.617 variants in the metroplex.

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“…Serially diluted samples were then added to 96-well plates, mixed with pseudotyped virus, and incubated at 37°C for 1 hour. Thereafter, 2×10 4 Huh-7 cells/100 μL were added to each well of the 96-well plate. Cells were then incubated at 37°C with 5% CO2.…”

Section: Methodsmentioning

confidence: 99%

Infectivity and antigenicity of SARS-CoV-2 B.1.617 variants

Wang¹,

Zhang²,

Li³

et al. 2021

Preprint

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SARS-CoV-2 has caused the COVID-19 pandemic. Recently, B.1.617 variants have been transmitted rapidly in India. The transmissibility, pathogenicity, and neutralization characteristics of these variants have received considerable interest. In this study, 22 pseudotyped viruses were constructed for B.1.617 variants and their corresponding single amino acid mutations. B.1.617 variants did not exhibit significant enhanced infectivity in human cells, but mutations T478K and E484Q in the receptor binding domain led to enhanced infectivity in mouse ACE2-overexpressing cells. Furin activities were slightly increased against B.1.617 variants and cell–cell fusion after infection of B.1.617 variants was enhanced. Furthermore, B.1.617 variants escaped neutralization by several mAbs, mainly because of mutations L452R, T478K, and E484Q in the receptor binding domain. The neutralization activities of sera from convalescent patients, inactivated vaccine-immunized volunteers, adenovirus vaccine-immunized volunteers, and SARS-CoV-2 immunized animals against pseudotyped B.1.617 variants were reduced by approximately twofold, compared with the D614G variant.

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Transmission, infectivity, and neutralization of a spike L452R SARS-CoV-2 variant

Cited by 488 publications

References 65 publications

SARS-CoV-2 Infectivity and Severity of COVID-19 According to SARS-CoV-2 Variants: Current Evidence

SARS-CoV-2 Infectivity and Severity of COVID-19 According to SARS-CoV-2 Variants: Current Evidence

Trajectory of Growth of SARS-CoV-2 Variants in Houston, Texas, January through May 2021 Based on 12,476 Genome Sequences

Infectivity and antigenicity of SARS-CoV-2 B.1.617 variants

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