Journal
NATURE
Volume 602, Issue 7896, Pages 307-+Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41586-021-04342-0
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Funding
- Swiss National Science Foundation (SNSF) [31CA30_196062, 31CA30_196644, 310030_173085, 310030_179260, 196383]
- European Commission, Marie Skodowska-Curie Innovative Training Network 'HONOURS' [721367]
- European Union Project ReCoVer [GA101003589]
- University of Bern
- German Federal Ministry of Food and Agriculture
- Deutsche Forschungsgemeinschaft (DFG) [453012513]
- Horizon 2020 project 'VEO' [874735]
- Swiss Federal Office of Public Health
- Swiss Federal Office of Food Safety and Veterinary Affairs
- Fondation Ancrage Bienfaisance du Groupe Pictet
- Fondation Privee des Hopitaux Universitaires de Geneve
- German Ministry of Research, VARIPath [01KI2021]
- Swiss National Science Foundation (SNF) [31CA30_196644, 31CA30_196062, 310030_179260] Funding Source: Swiss National Science Foundation (SNF)
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Experimental assessments of major VOCs show that Alpha and Beta variants have a higher affinity for the human ACE2 receptor compared to the progenitor variant. Competition experiments demonstrate that Alpha has a clear fitness advantage over wt-S-614G in ferrets and mouse models.
Emerging variants of concern (VOCs) are driving the COVID-19 pandemic(1,2). Experimental assessments of replication and transmission of major VOCs and progenitors are needed to understand the mechanisms of replication and transmission of VOCs3. Here we show that the spike protein (S) from Alpha (also known as B.1.1.7) and Beta (B.1.351) VOCs had a greater affinity towards the human angiotensin-converting enzyme 2 (ACE2) receptor than that of the progenitor variant S(D614G) in vitro. Progenitor variant virus expressing S(D614G) (wt-S-614G) and the Alpha variant showed similar replication kinetics in human nasal airway epithelial cultures, whereas the Beta variant was outcompeted by both. In vivo, competition experiments showed a clear fitness advantage of Alpha over wt-S-614G in ferrets and two mouse models-the substitutions in S were major drivers of the fitness advantage. In hamsters, which support high viral replication levels, Alpha and wt-S-614G showed similar fitness. By contrast, Beta was outcompeted by Alpha and wt-S-614G in hamsters and in mice expressing human ACE2. Our study highlights the importance of using multiple models to characterize fitness of VOCs and demonstrates that Alpha is adapted for replication in the upper respiratory tract and shows enhanced transmission in vivo in restrictive models, whereas Beta does not overcome Alpha or wt-S-614G in naive animals.
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