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

Cristina Andrés, Damir Garcia-Cehic, Josep Gregori, Maria Piñana, Francisco Rodriguez-Frias, Mercedes Guerrero-Murillo, Juliana Esperalba, Ariadna Rando, Lidia Goterris, Maria Gema Codina, Susanna Quer, Maria Carmen Martín, Magda Campins, Ricard Ferrer, Benito Almirante, Juan Ignacio Esteban, Tomás Pumarola, Andrés Antón*, Josep Quer*

*Autor correspondiente de este trabajo

Producción científica: Contribución a una revistaArtículoInvestigaciónrevisión exhaustiva

45 Citas (Scopus)

Resumen

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.
Idioma originalInglés
Páginas (desde-hasta)1900-1911
Número de páginas12
PublicaciónEmerging Microbes and Infections
Volumen9
N.º1
DOI
EstadoPublicación electrónica previa a su impresión - 2 sept 2020

Palabras clave

  • SARS-CoV-2
  • Deletions
  • Quasispecies
  • NGS
  • Respiratory virus
  • Diversity

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