PT  - JOURNAL ARTICLE
AU  - M. Zeeshan Chaudhry
AU  - Kathrin Eschke
AU  - Martina Grashoff
AU  - Leila Abassi
AU  - Yeonsu Kim
AU  - Linda Brunotte
AU  - Stephan Ludwig
AU  - Željka Mačak Šafranko
AU  - Ivan-Christian Kurolt
AU  - Alemka Markotić
AU  - Andrea Kröger
AU  - Frank Klawonn
AU  - Luka Cicin-Sain
TI  - SARS-CoV-2 Quasispecies Mediate Rapid Virus Evolution and Adaptation
AID  - 10.1101/2020.08.10.241414
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.08.10.241414
4099  - http://biorxiv.org/content/early/2020/08/10/2020.08.10.241414.short
4100  - http://biorxiv.org/content/early/2020/08/10/2020.08.10.241414.full
AB  - The pandemic spread of SARS-CoV-2 and the resulting global healthcare emergency warrants a better understanding of its biology. The potential of SARS-CoV-2 evolution to create novel dangerous variants remains underexplored. Thus, we passaged SARS-CoV-2 in defined conditions and determined its genomic adaptation dynamics. We demonstrate the presence of remarkably stable SARS-CoV-2 quasispecies. We further show that the quasispecies nature of the virus population ensured rapid adaptation of the spike PRRARS motif upon passaging in Vero cells. On the other hand, SARS-CoV-2 replication in TMPRSS2 expressing cells led to a reverse mutation at the same site. We observed the emergence of novel mutations in envelope protein upon virus culture in Calu-3 and Caco-2 cells. Finally, we show that the heparan sulfate-binding motif (PRRARS) of the SARS-CoV-2 S protein acted as a determinant of negative growth selection. Overall, our research has far-reaching implications for development of antiviral strategies, suggesting viral quasispecies may facilitate rapid emergence of escape mutants under selection pressure, such as the treatment with antivirals against SARS-CoV-2.Competing Interest StatementThe authors have declared no competing interest.