Dataset Information

Emergence and Spread of a B.1.1.28-Derived P.6 Lineage with Q675H and Q677H Spike Mutations in Uruguay.

ABSTRACT: Uruguay controlled the viral dissemination during the first nine months of the SARS-CoV-2 pandemic. Unfortunately, towards the end of 2020, the number of daily new cases exponentially increased. Herein, we analyzed the country-wide genetic diversity of SARS-CoV-2 between November 2020 and April 2021. We identified that the most prevalent viral variant during the first epidemic wave in Uruguay (December 2020-February 2021) was a B.1.1.28 sublineage carrying Spike mutations Q675H + Q677H, now designated as P.6, followed by lineages P.2 and P.7. P.6 probably arose around November 2020, in Montevideo, Uruguay's capital department, and rapidly spread to other departments, with evidence of further local transmission clusters; it also spread sporadically to the USA and Spain. The more efficient dissemination of lineage P.6 with respect to P.2 and P.7 and the presence of mutations (Q675H and Q677H) in the proximity of the key cleavage site at the S1/S2 boundary suggest that P.6 may be more transmissible than other lineages co-circulating in Uruguay. Although P.6 was replaced by the variant of concern (VOC) P.1 as the predominant lineage in Uruguay since April 2021, the monitoring of the concurrent emergence of Q675H + Q677H in VOCs should be of worldwide interest.

SUBMITTER: Rego N

PROVIDER: S-EPMC8473254 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

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Publications

Emergence and Spread of a B.1.1.28-Derived P.6 Lineage with Q675H and Q677H Spike Mutations in Uruguay.

Rego Natalia N Salazar Cecilia C Paz Mercedes M Costábile Alicia A Fajardo Alvaro A Ferrés Ignacio I Perbolianachis Paula P Fernández-Calero Tamara T Noya Veronica V Machado Matias R MR Brandes Mariana M Arce Rodrigo R Arleo Mailen M Possi Tania T Reyes Natalia N Bentancor María Noel MN Lizasoain Andrés A Bortagaray Viviana V Moller Ana A Chappos Odhille O Nin Nicolas N Hurtado Javier J Duquía Melissa M González Maria Belén MB Griffero Luciana L Méndez Mauricio M Techera Maria Pía MP Zanetti Juan J Pereira Emiliano E Rivera Bernardina B Maidana Matías M Alonso Martina M Smircich Pablo P Arantes Ighor I Mir Daiana D Alonso Cecilia C Medina Julio J Albornoz Henry H Colina Rodney R Bello Gonzalo G Moreno Pilar P Moratorio Gonzalo G Iraola Gregorio G Spangenberg Lucía L

Viruses 20210910 9

Uruguay controlled the viral dissemination during the first nine months of the SARS-CoV-2 pandemic. Unfortunately, towards the end of 2020, the number of daily new cases exponentially increased. Herein, we analyzed the country-wide genetic diversity of SARS-CoV-2 between November 2020 and April 2021. We identified that the most prevalent viral variant during the first epidemic wave in Uruguay (December 2020-February 2021) was a B.1.1.28 sublineage carrying Spike mutations Q675H + Q677H, now desi ...[more]

PMID: 34578382

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Project description:BackgroundThe emergence of SARS-CoV-2 underscores the need to better understand the evolutionary processes that drive the emergence and adaptation of zoonotic viruses in humans. In the betacoronavirus genus, which also includes SARS-CoV and MERS-CoV, recombination frequently encompasses the receptor binding domain (RBD) of the Spike protein, which is responsible for viral binding to host cell receptors. In this work, we reconstruct the evolutionary events that have accompanied the emergence of SARS-CoV-2, with a special emphasis on the RBD and its adaptation for binding to its receptor, human ACE2.MethodsBy means of phylogenetic and recombination analyses, we found evidence of a recombination event in the RBD involving ancestral linages to both SARS-CoV and SARS-CoV-2. We then assessed the effect of this recombination at protein level by reconstructing the RBD of the closest ancestors to SARS-CoV-2, SARS-CoV, and other Sarbecoviruses, including the most recent common ancestor of the recombining clade. The resulting information was used to measure and compare, in silico, their ACE2-binding affinities using the physics-based trRosetta algorithm.ResultsWe show that, through an ancestral recombination event, SARS-CoV and SARS-CoV-2 share an RBD sequence that includes two insertions (positions 432-436 and 460-472), as well as the variants 427N and 436Y. Both 427N and 436Y belong to a helix that interacts directly with the human ACE2 (hACE2) receptor. Reconstruction of ancestral states, combined with protein-binding affinity analyses, suggests that the recombination event involving ancestral strains of SARS-CoV and SARS-CoV-2 led to an increased affinity for hACE2 binding and that alleles 427N and 436Y significantly enhanced affinity as well.ConclusionsWe report an ancestral recombination event affecting the RBD of both SARS-CoV and SARS-CoV-2 that was associated with an increased binding affinity to hACE2. Structural modeling indicates that ancestors of SARS-CoV-2 may have acquired the ability to infect humans decades ago. The binding affinity with the human receptor would have been subsequently boosted in SARS-CoV and SARS-CoV-2 through further mutations in RBD.

Dataset Information

Emergence and Spread of a B.1.1.28-Derived P.6 Lineage with Q675H and Q677H Spike Mutations in Uruguay.

Publications

Emergence and Spread of a B.1.1.28-Derived P.6 Lineage with Q675H and Q677H Spike Mutations in Uruguay.

Similar Datasets

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