SARS CoV-2 variant B.1.617.1 is highly pathogenic in hamsters than B.1 variant

Yadav, Pragya D; Mohandas, Sreelekshmy; Shete, Anita M.; Nyayanit, Dimpal A; Gupta, Nivedita; Patil, Deepak Y.; Sapkal, Gajanan; Potdar, Varsha; Kadam, Manoj; Kumar, Abhimanyu; Kumar, Sanjay; Suryavanshi, Deepak; Mote, Chandrashekhar; Abraham, Priya; Panda, Samiran; Bhargava, Balram

doi:10.1101/2021.05.05.442760

Cited by 57 publications

(52 citation statements)

References 21 publications

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“…In vitro, we find modestly reduced sensitivity of the ancestral B.1.617.1 spike protein to BNT162b2 mRNA vaccine-elicited antibodies that is similar in magnitude to the loss of sensitivity conferred by L452R or E484Q alone. Furthermore we show that the P681R mutation significantly augments syncytium formation upon the B.1.617.1 spike protein, potentially contributing to increased pathogenesis observed in hamsters 16 and high growth rates observed in humans.…”

Section: Introductionmentioning

confidence: 77%

SARS-CoV-2 B.1.617.2 Delta variant replication, sensitivity to neutralising antibodies and vaccine breakthrough

Mlčochová¹,

Kemp²,

Dhar³

et al. 2021

Preprint

106

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The B.1.617 variant emerged in the Indian state of Maharashtra in late 2020 and has spread throughout India and to at least 40 countries. There have been fears that two key mutations seen in the receptor binding domain L452R and E484Q would have additive effects on evasion of neutralising antibodies. Here we delineate the phylogenetics of B.1.617 and spike mutation frequencies, in the context of others bearing L452R. The defining mutations in B.1.617.1 spike are L452R and E484Q in the RBD that interacts with ACE2 and is the target of neutralising antibodies. All B.1.617 viruses have the P681R mutation in the polybasic cleavage site region in spike. We report that B.1.617.1 spike bearing L452R, E484Q and P681R mediates entry into cells with slightly reduced efficiency compared to Wuhan-1. This spike confers modestly reduced sensitivity to BNT162b2 mRNA vaccine-elicited antibodies that is similar in magnitude to the loss of sensitivity conferred by L452R or E484Q alone. Furthermore we show that the P681R mutation significantly augments syncytium formation upon the B.1.617.1 spike protein, potentially contributing to increased pathogenesis observed in hamsters and infection growth rates observed in humans.

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Section: Introductionmentioning

confidence: 77%

SARS-CoV-2 B.1.617.2 Delta variant replication, sensitivity to neutralising antibodies and vaccine breakthrough

Mlčochová¹,

Kemp²,

Dhar³

et al. 2021

Preprint

106

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“…In January 2021, the mutation Q1071H emerged, giving rise to three new sub-clusters (B.1.617:A, B.1.617:B, B.1.617C) [55]. There are seven additional mutations (T19R, K77T, T95I, E154K, N440K, T478K, H1101D) that occur with varying frequencies in the B.1.617 sequence background [55] [73]. Antibodies and sera from vaccinated people are, however, able to neutralise a pseudotyped VSV virus carrying the B.1.617 spike with the mutations R21T, E154K, Q218H, L452R, E484Q, D614G, P681R, and H1101D (GISAID Accession ID: PI_ISL_1360382) [74].…”

Section: The Danish B11298 Variantmentioning

confidence: 99%

The Spike of Concern—The Novel Variants of SARS-CoV-2

Winger

Caspari

2021

Viruses

107

116

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The high sequence identity of the first SARS-CoV-2 samples collected in December 2019 at Wuhan did not foretell the emergence of novel variants in the United Kingdom, North and South America, India, or South Africa that drive the current waves of the pandemic. The viral spike receptor possesses two surface areas of high mutagenic plasticity: the supersite in its N-terminal domain (NTD) that is recognised by all anti-NTD antibodies and its receptor binding domain (RBD) where 17 residues make contact with the human Ace2 protein (angiotensin I converting enzyme 2) and many neutralising antibodies bind. While NTD mutations appear at first glance very diverse, they converge on the structure of the supersite. The mutations within the RBD, on the other hand, hone in on only a small number of key sites (K417, L452, E484, N501) that are allosteric control points enabling spike to escape neutralising antibodies while maintaining or even gaining Ace2-binding activity. The D614G mutation is the hallmark of all variants, as it promotes viral spread by increasing the number of open spike protomers in the homo-trimeric receptor complex. This review discusses the recent spike mutations as well as their evolution.

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“…We also identified seven patients infected with B.1.617family variants, genotypes now causing extensive disease in India. [43][44][45] A key finding from our study was the very rapid trajectory of VOC B.1.1.7 in metropolitan Houston, an area with a population size of approximately 7 million. Several investigators have reported previously that patients infected with the B.1.1.7 VOC have significantly lower Ct values on initial diagnosis, but this has not been a universal finding.…”

Section: Discussionmentioning

confidence: 64%

“…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: 63%

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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SARS CoV-2 variant B.1.617.1 is highly pathogenic in hamsters than B.1 variant

Cited by 57 publications

References 21 publications

SARS-CoV-2 B.1.617.2 Delta variant replication, sensitivity to neutralising antibodies and vaccine breakthrough

SARS-CoV-2 B.1.617.2 Delta variant replication, sensitivity to neutralising antibodies and vaccine breakthrough

The Spike of Concern—The Novel Variants of SARS-CoV-2

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

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