PT  - JOURNAL ARTICLE
AU  - Jingsong Zhang
AU  - Yang Zhang
AU  - Junyan Kang
AU  - Shuiye Chen
AU  - Yongqun He
AU  - Benhao Han
AU  - Mofang Liu
AU  - Lina Lu
AU  - Li Li
AU  - Zhigang Yi
AU  - Luonan Chen
TI  - Potential transmission chains of variant B.1.1.7 and co-mutations of SARS-CoV-2
AID  - 10.1101/2021.04.16.440141
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.04.16.440141
4099  - http://biorxiv.org/content/early/2021/04/20/2021.04.16.440141.short
4100  - http://biorxiv.org/content/early/2021/04/20/2021.04.16.440141.full
AB  - The presence of SARS-CoV-2 mutants, including the emerging variant B.1.1.7, has raised great concerns in terms of pathogenesis, transmission, and immune escape. Characterizing SARS-CoV-2 mutations, evolution, and effects on infectivity and pathogenicity is crucial to the design of antibody therapies and surveillance strategies. Here we analyzed 454,443 SARS-CoV-2 spike genes/proteins and 14,427 whole-genome sequences. We demonstrated that the early variant B.1.1.7 may not have evolved spontaneously in the United Kingdom or within human populations. Our extensive analyses suggested that Canidae, Mustelidae or Felidae, especially the Canidae family (for example, dog) could be a possible host of the direct progenitor of variant B.1.1.7. An alternative hypothesis is that the variant was simply yet to be sampled. Notably, the SARS-CoV-2 whole genome represents a large number of potential co-mutations with very strong statistical significances (p value<E– 44). In addition, we used an experimental SARS-CoV-2 reporter replicon system to introduce the dominant co-mutations NSP12_c14408t, 5’UTR_c241t, and NSP3_c3037t into the viral genome, and to monitor the effect of the mutations on viral replication. Our experimental results demonstrated that the co-mutations significantly attenuated the viral replication. The study provides valuable clues for discovering the transmission chains of variant B.1.1.7 and understanding the evolutionary process of SARS-CoV-2.Competing Interest StatementThe authors have declared no competing interest.