Attenuated SARS-CoV-2 variants with deletions at the S1/S2 junction

Emerg Microbes Infect. 2020 Dec;9(1):837-842. doi: 10.1080/22221751.2020.1756700.

Abstract

The emergence of SARS-CoV-2 has led to the current global coronavirus pandemic and more than one million infections since December 2019. The exact origin of SARS-CoV-2 remains elusive, but the presence of a distinct motif in the S1/S2 junction region suggests the possible acquisition of cleavage site(s) in the spike protein that promoted cross-species transmission. Through plaque purification of Vero-E6 cultured SARS-CoV-2, we found a series of variants which contain 15-30-bp deletions (Del-mut) or point mutations respectively at the S1/S2 junction. Examination of the original clinical specimen from which the isolate was derived, and 26 additional SARS-CoV-2 positive clinical specimens, failed to detect these variants. Infection of hamsters shows that one of the variants (Del-mut-1) which carries deletion of 10 amino acids (30bp) does not cause the body weight loss or more severe pathological changes in the lungs that is associated with wild type virus infection. We suggest that the unique cleavage motif promoting SARS-CoV-2 infection in humans may be under strong selective pressure, given that replication in permissive Vero-E6 cells leads to the loss of this adaptive function. It would be important to screen the prevalence of these variants in asymptomatic infected cases. The potential of the Del-mut variants as an attenuated vaccine or laboratory tool should be evaluated.

Keywords: COVID-19; Coronavirus; SARS-CoV-2; Spike S1/S2 mutant; Spike mutant.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • COVID-19
  • Cell Line
  • Chlorocebus aethiops
  • Coronavirus Infections / pathology*
  • Coronavirus Infections / virology
  • Disease Models, Animal*
  • Female
  • Host Specificity
  • Humans
  • Lung / pathology
  • Male
  • Mesocricetus*
  • Pandemics
  • Pneumonia, Viral / pathology*
  • Pneumonia, Viral / virology
  • SARS Virus / genetics*
  • SARS Virus / growth & development
  • SARS Virus / isolation & purification
  • SARS Virus / pathogenicity*
  • Sequence Deletion*
  • Spike Glycoprotein, Coronavirus / chemistry
  • Spike Glycoprotein, Coronavirus / genetics*
  • Vero Cells
  • Virulence

Substances

  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2

Grant support

This study is partly supported by the Theme-Based Research Scheme (T11/707/15) of the University Grant Committee, Hong Kong Special Administrative Region; the Sanming Project of Medicine in Shenzhen [grant number SZSM201911014), and the High-Level Hospital Program, Health Commission of Guangdong Province as well as Coalition for Epidemic Preparedness Innovations (CEPI) seed funding for the Outbreak Response to Novel Coronavirus (COVID-19).