Genomic characterization of a novel SARS-CoV-2 lineage from Rio de Janeiro, Brazil

Voloch, Carolina M; F, Ronaldo da Silva; Almeida, Luiz Gonzaga Paula de; Cardoso, Cynthia Chester; Brustolini, Otávio J. B.; Gerber, Alexandra Lehmkuhl; Guimarães, Ana P.; Mariani, Diana; Costa, Raissa Mirella da; Ferreira, Orlando C.; Workgroup, Covid Ufrj; LNCC-Workgroup,; Cavalcanti, Adriana Cony; Frauches, Thiago Silva; Mello, Claudia Maria Braga de; Galliez, Rafael Mello; Faffe, Débora S.; Castiñeiras, Terezinha Marta Pereira Pinto; Tanuri, Amílcar; Vasconcelos, Ana Tereza Ribeiro de

doi:10.1101/2020.12.23.20248598

Cited by 192 publications

(212 citation statements)

References 27 publications

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“…In particular, a lot of attention has been focused on RBD mutation E484K, which has emerged in multiple independently SARS-CoV-2 lineages 63, 64 and can alter the antigenicity of the spike protein [65][66][67] . Another naturally occurring RBD mutation, K417N, which has emerged in South Africa and Brazil (B.1.351 lineage and B.1.1.28, respectively) 63, 64,68 , has recently been shown to also alter antigenicity of the spike protein 66,[69][70][71] . Consistently, we found that K417N dramatically decreased the binding of COV107-23 (clonotype 1) and COVD21-C8 (clonotype 2)…”

Section: Discussionmentioning

confidence: 99%

Sequence signatures of two IGHV3-53/3-66 public clonotypes to SARS-CoV-2 receptor binding domain

Tan

Yuan

Kuzelka

et al. 2021

Preprint

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Since the COVID-19 pandemic onset, the antibody response to SARS-CoV-2 has been extensively characterized. Antibodies to the receptor binding domain (RBD) on the spike protein are frequently encoded by IGHV3-53/3-66 with a short CDR H3. Germline-encoded sequence motifs in CDRs H1 and H2 play a major role, but whether any common motifs are present in CDR H3, which is often critical for binding specificity, have not been elucidated. Here, we identify two public clonotypes of IGHV3-53/3-66 RBD antibodies with a 9-residue CDR H3 that pair with different light chains. Distinct sequence motifs on CDR H3 are present in the two public clonotypes that appear to be related to differential light chain pairing. Additionally, we show that Y58F is a common somatic hypermutation that results in increased binding affinity of IGHV3-53/3-66 RBD antibodies with a short CDR H3. Overall, our results advance fundamental understanding of the antibody response to SARS-CoV-2.

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Section: Discussionmentioning

confidence: 99%

Sequence signatures of two IGHV3-53/3-66 public clonotypes to SARS-CoV-2 receptor binding domain

Tan

Yuan

Kuzelka

et al. 2021

Preprint

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“…Its appearance is likely to have arisen independently (Faria et al, 2021) . In Brazil, the E484K mutation (glutamic acid to lysine substitution at amino acid 484) also arose independently and was identified in Rio de Janeiro state (Southeast Brazil) in early-October in P.2 lineage (Voloch et al, 2020) .…”

Section: Introductionmentioning

confidence: 99%

E484K as an innovative phylogenetic event for viral evolution: Genomic analysis of the E484K spike mutation in SARS-CoV-2 lineages from Brazil

Ferrareze

Franceschi

Mayer

et al. 2021

Preprint

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The COVID-19 pandemic caused by SARS-CoV-2 has affected millions of people since its beginning in 2019. The propagation of new lineages and the discovery of key mechanisms adopted by the virus to overlap the immune system are central topics for the entire public health policies, research and disease management. Since the second semester 2020, the mutation E484K has been progressively found in the Brazilian territory, composing different lineages over time. It brought multiple concerns related to the risk of reinfection and the effectiveness of new preventive and treatment strategies due to the possibility of escaping from neutralizing antibodies. To better characterize the current scenario we performed genomic and phylogenetic analyses of the E484K mutated genomes sequenced from Brazilian samples in 2020. From October, 2020, 43.9% of the sequenced genomes present the E484K mutation, which was identified in three different lineages (P1, P2 and B.1.1.33) in four Brazilian regions. We also evaluated the presence of E484K associated mutations and identified selective pressures acting on the spike protein, leading us to some insights about adaptive and purifying selection driving the virus evolution.

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“…After more than a year of the COVID-19 pandemic, new circulating variants of SARS-CoV-2 have been described that show resistance against the immune response of previously immunized individuals 1,2 or available therapeutics 3,4 . In many regions around the globe, governments are implementing lock-down measures to contain rapidly spreading SARS-CoV-2 spike variants associated with increased transmissibility 5 .…”

Section: Introductionmentioning

confidence: 99%

“…Recently identified variants in the UK (B.1.1.7 lineage), South Africa (B.1.351 lineage) 6 and Brazil (P.1. lineage) 2 share mutations on the spike protein, which have evolved independently.…”

Section: Introductionmentioning

confidence: 99%

Ensovibep, a novel trispecific DARPin candidate that protects against SARS-CoV-2 variants

Rothenberger

Walser

Malvezzi

et al. 2021

Preprint

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The SARS-CoV-2 virus responsible for the COVID-19 pandemic has so far infected more than 100 million people globally, and continues to undergo genomic evolution. Emerging SARS-CoV-2 variants show increased infectivity and may lead to resistance against immune responses of previously immunized individuals or existing therapeutics, especially antibody-based therapies. Several monoclonal antibody therapeutics authorized for emergency use or in development start to lose potency against various SARS-CoV-2 variants. Cocktails of two different monoclonal antibodies constitute a promising approach to protect against such variants as long as both antibodies are potent, but come with increased development complexity and therefore cost. As an alternative, we developed two multi-specific DARPin® therapeutics, each combining three independent DARPin® domains binding the SARS-CoV-2 spike protein in one molecule, to potently neutralize the virus and overcome virus escape. Here, we show in a panel of in vitro studies that both multi-specific DARPin® therapeutics, ensovibep (MP0420) and MP0423, are highly potent against the new circulating SARS-CoV-2 variants B.1.1.7 (UK variant) and B.1.351 (South African variant) and the most frequent emerging mutations in the spike protein. Additionally, viral passaging experiments show potent protection by ensovibep and MP0423 against development of escape mutations. Furthermore, we demonstrate that the cooperative binding of the individual modules in a multi-specific DARPin® antiviral is key for potent virus inhibition and protection from escape variants. These results, combined with the relatively small size and high production yields of DARPin® molecules, suggests ensovibep and MP0423 as superior alternatives to monoclonal antibody cocktails for global supply and demonstrate the strength of the DARPin® platform for achieving potent and lasting virus inhibition for SARS-CoV-2 and possibly other viruses.

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Genomic characterization of a novel SARS-CoV-2 lineage from Rio de Janeiro, Brazil

Cited by 192 publications

References 27 publications

Sequence signatures of two IGHV3-53/3-66 public clonotypes to SARS-CoV-2 receptor binding domain

Sequence signatures of two IGHV3-53/3-66 public clonotypes to SARS-CoV-2 receptor binding domain

E484K as an innovative phylogenetic event for viral evolution: Genomic analysis of the E484K spike mutation in SARS-CoV-2 lineages from Brazil

Ensovibep, a novel trispecific DARPin candidate that protects against SARS-CoV-2 variants

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