Naturally occurring SARS-CoV-2 gene deletions close to the spike S1/S2 cleavage site in the viral quasispecies of COVID19 patients

The SARS-CoV-2 spike (S) protein, the viral mediator for binding and entry into the host cell, has sparked great interest as a target for vaccine development and treatments with neutralizing antibodies. Initial data suggest that the virus has low mutation rates, but its large genome could facilitate...

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Detalhes bibliográficos
Autores: Andrés, Cristina|||0000-0002-3200-0895, Garcia-Cehic, D.|||0000-0002-0009-038X, Gregori i Font, Josep|||0000-0002-4253-8015, Piñana, Maria|||0000-0002-4766-2613, Rodríguez Frías, Francisco|||0000-0002-9128-7013, Guerrero Murillo, Mercedes|||0000-0002-5556-2460, Esperalba, Juliana|||0000-0003-1326-1341, Rando-Segura, Ariadna|||0000-0003-4555-7286, Goterris, Lidia|||0000-0003-1471-4461, Codina, María Gema|||0000-0002-5313-5086, Quer, Susanna, Martín, Maria Carmen, Campins Martí, Magda|||0000-0002-8841-6195, Ferrer, Ricard|||0000-0002-4859-4747, Almirante Gragera, Benito|||0000-0002-1189-2361, Esteban Mur, Juan Ignacio|||0000-0001-5085-917X, Pumarola Suñé, Tomàs|||0000-0002-5171-7461, Antón Pagarolas, Andrés, 1976-|||0000-0002-1476-0815, Quer, Josep|||0000-0003-0014-084X
Formato: artículo
Fecha de publicación:2020
País:España
Recursos:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:244121
Acesso em linha:https://ddd.uab.cat/record/244121
https://dx.doi.org/urn:doi:10.1080/22221751.2020.1806735
Access Level:acceso abierto
Palavra-chave:COVID-19
SARS-CoV-2
Deletions
Quasispecies
NGS
Respiratory virus
Diversity
Descrição
Resumo:The SARS-CoV-2 spike (S) protein, the viral mediator for binding and entry into the host cell, has sparked great interest as a target for vaccine development and treatments with neutralizing antibodies. Initial data suggest that the virus has low mutation rates, but its large genome could facilitate recombination, insertions, and deletions, as has been described in other coronaviruses. Here, we deep-sequenced the complete SARS-CoV-2 S gene from 18 patients (10 with mild and 8 with severe COVID-19), and found that the virus accumulates deletions upstream and very close to the S1/S2 cleavage site (PRRAR/S), generating a frameshift with appearance of a stop codon. These deletions were found in a small percentage of the viral quasispecies (2.2%) in samples from all the mild and only half the severe COVID-19 patients. Our results suggest that the virus may generate free S1 protein released to the circulation. We suggest that natural selection has favoured a "Don't burn down the house" strategy, in which free S1 protein may compete with viral particles for the ACE2 receptor, thus reducing the severity of the infection and tissue damage without losing transmission capability.

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