Spread of Gamma (P.1) Sub-Lineages Carrying Spike Mutations Close to the Furin Cleavage Site and Deletions in the N-Terminal Domain Drives Ongoing Transmission of SARS-CoV-2 in Amazonas, Brazil

dc.creatorNaveca, Felipe
dc.creatorNascimento, Valdinete
dc.creatorSouza, Victor
dc.creatorCorado, André de Lima
dc.creatorNascimento, Fernanda
dc.creatorSilva, George
dc.creatorMejía, Matilde Contreras
dc.creatorBrandão, Maria Júlia
dc.creatorCosta, Àgatha
dc.creatorDuarte, Débora
dc.creatorPessoa, Karina
dc.creatorJesus, Michele
dc.creatorGonçalves, Luciana
dc.creatorFernanades, Cristiano
dc.creatorMattos, Tirza
dc.creatorAbdala, Ligia
dc.creatorSantos, João Hugo
dc.creatorMartins, Alex
dc.creatorChui, Fabiola Mendonça
dc.creatorVal, Fernando Fonseca
dc.creatorMelo, Gisely Cardoso de
dc.creatorXavier, Mariana Siimão
dc.creatorSampaio, Vanderson de Souza
dc.creatorMourão, Maria Paula
dc.creatorLacerda, Marcus Vinicius
dc.creatorBatista, Érika Lopes Rocha
dc.creatorMagalhães, Alessandro Leonardo Álvares
dc.creatorDábilla, Nathânia
dc.creatorPereira, Lucas Carlos Gomes
dc.creatorVinhal, Fernando
dc.creatorMiyajima, Fabio
dc.creatorDias, Fernando Braga Stehling
dc.creatorSantos, Eduardo Ruback dos
dc.creatorCoêlho, Danilo
dc.creatorFerraz, Matheus
dc.creatorLins, Roberto
dc.creatorWallau, Gabriel Luz
dc.creatorDelatorre, Edson
dc.creatorGräf, Tiago
dc.creatorSiqueira, Marilda Agudo Mendonça Teixeira de
dc.creatorResende, Paola Cristina
dc.creatorBello, Gonzalo
dc.date2022-03-08T18:48:03Z
dc.date2022-03-08T18:48:03Z
dc.date2022
dc.date.accessioned2023-09-26T20:11:08Z
dc.date.available2023-09-26T20:11:08Z
dc.identifierNAVECA, Felipe Gomes et al. Spread of Gamma (P.1) Sub-Lineages Carrying Spike Mutations Close to the Furin Cleavage Site and Deletions in the N-Terminal Domain Drives Ongoing Transmission of SARS-CoV-2 in Amazonas, Brazil. Microbiology Spectrum, v. 10, n. 1, p. 1 - 17, Feb. 2022.
dc.identifier2165-0497
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/51623
dc.identifier10.1128/spectrum.02366-21
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8850747
dc.descriptionA Rede Genômica Fiocruz é formada por especialistas de todas as unidades da Fundação no país e de institutos parceiros que se empenham diariamente em gerar dados mais robustos sobre o comportamento do SARS-Cov-2 e contribuir para um melhor preparo do país no enfrentamento da pandemia em termos de diagnóstico mais precisos e vacinas eficazes. Saiba mais sobre a Rede Genômica Fiocruz em: http://www.genomahcov.fiocruz.br/
dc.descriptionThe Amazonas was one of the most heavily affected Brazilian states by the COVID-19 epidemic. Despite a large number of infected people, particularly during the second wave associated with the spread of the Variant of Concern (VOC) Gamma (lineage P.1), SARS-CoV-2 continues to circulate in the Amazonas. To understand how SARS-CoV-2 persisted in a human population with a high immunity barrier, we generated 1,188 SARS-CoV-2 whole-genome sequences from individuals diagnosed in the Amazonas state from 1st January to 6th July 2021, of which 38 were vaccine breakthrough infections. Our study reveals a sharp increase in the relative prevalence of Gamma plus (P.11) variants, designated Pango Lineages P.1.3 to P.1.6, harboring two types of additional Spike changes: deletions in the N-terminal (NTD) domain (particularly D144 or D141-144) associated with resistance to anti-NTD neutralizing antibodies or mutations at the S1/S2 junction (N679K or P681H) that probably enhance the binding affinity to the furin cleavage site, as suggested by our molecular dynamics simulations. As lineages P.1.4 (S:N679K) and P.1.6 (S:P681H) expanded (Re . 1) from March to July 2021, the lineage P.1 declined (Re , 1) and the median Ct value of SARS-CoV-2 positive cases in Amazonas significantly decreases. Still, we did not find an increased incidence of P.11 variants among breakthrough cases of fully vaccinated patients (71%) in comparison to unvaccinated individuals (93%). This evidence supports that the ongoing endemic transmission of SARS-CoV-2 in the Amazonas is driven by the spread of new local Gamma/P.1 sublineages that are more transmissible, although not more efficient to evade vaccine-elicited immunity than the parental VOC. Finally, as SARS-CoV-2 continues to spread in human populations with a declining density of susceptible hosts, the risk of selecting more infectious variants or antibody evasion mutations is expected to increase. IMPORTANCE The continuous evolution of SARS-CoV-2 is an expected phenomenon that will continue to happen due to the high number of cases worldwide. The present study analyzed how a Variant of Concern (VOC) could still circulate in a population hardly affected by two COVID-19 waves and with vaccination in progress. Our results showed that the answer behind that was a new generation of Gamma-like viruses, which emerged locally carrying mutations that made it more transmissible and more capable of spreading, partially evading prior immunity triggered by natural infections or vaccines. With thousands of new cases daily, the current pandemics scenario suggests that SARS-CoV-2 will continue to evolve and efforts to reduce the number of infected subjects, including global equitable access to COVID-19 vaccines, are mandatory. Thus, until the end of pandemics, the SARS-CoV-2 genomic surveillance will be an essential tool to better understand the drivers of the viral evolutionary process.
dc.formatapplication/pdf
dc.formatapplication/pdf
dc.languageeng
dc.publisherAmerican Society for Microbiology
dc.rightsopen access
dc.subjectCOVID-19
dc.subjectSARS-CoV-2
dc.subjectCoronavírus
dc.subjectEvolução do Vírus
dc.subjectVariante Gamma
dc.subjectRede Genômica Fiocruz
dc.subjectGENOMAHCOV
dc.subjectCOVID-19
dc.subjectSARS-CoV-2
dc.subjectCoronavirus
dc.subjectVirus evolution
dc.subjectVariant gamma
dc.subjectBrasil
dc.titleSpread of Gamma (P.1) Sub-Lineages Carrying Spike Mutations Close to the Furin Cleavage Site and Deletions in the N-Terminal Domain Drives Ongoing Transmission of SARS-CoV-2 in Amazonas, Brazil
dc.typeArticle


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