(Source: DHS Science and Technology, Master Question List for COVID-19 (caused by SARS-CoV-2), Weekly Report, 18 March 2020)

Genomics (Part 12)

What is known? 

• There have been no documented cases of SARS-CoV-2 prior to December 2019.
• Preliminary genomic analyses indicate that the first human cases of SARS-CoV-2 appeared between 10/19/2019 and 12/17/2019.^1-3
• The mutation rate of SARS-CoV-2 is estimated to be similar to that of other RNA viruses (such as SARS, Ebola, Zika), and is currently estimated as 1.04x10^-3substitutions per site per year (N = 116 genomes).⁴
• Preliminary phylogenetic analysis identified a very close genetic similarity between SARS-CoV-2 and a Bat coronavirus (RaTG13) that was isolated from Yunnan Province, China. It has suggested that SARS-CoV-2 originated from bats.⁵
• Pangolin coronaviruses are also closely related to both SARS-CoV-2 and the closely related Bat coronavirus (RaTG13). Phylogenetic analysis revealed that SARS-CoV-2 is of bat origin, but is closely related to pangolin coronavirus.^6,7
• The Spike protein of SARS-CoV-2, known to mediate entry into host cells, and the major determinant of host range, is very similar to the Spike protein of SARS-CoV.⁸ The rest of the genome is more closely related to two separate bat⁸and pangolin⁷ coronavirus.
• Analysis of SARS-CoV-2 sequences from Singapore identified a large nucleotide (382 bp) deletion in ORF-8 that may give rise to an attenuated (less virulent) phenotype.⁹

What do we need to know?

• Are there similar genomic differences in the progression of coronavirus strains from bat to intermediate species to human?
• Are there different strains or clades of circulating virus? If yes, do they differ in virulence?

References

1. Anderson, K., Estimates of the clock and TMRCA for 2019-nCoV based on 27 genomes. http://virological.org/t/clock-and-tmrca-based-on-27-genomes/347(accessed 01/26/2020).
2. Bedford, T.; Neher, R., Genomic epidemiology of novel coronavirus (nCoV) using data from GISAID. https://nextstrain.org/ncov.
3. Rambaut, A., Phylodynamic analysis of nCoV-2019 genomes - 27-Jan-2020. http://virological.org/t/phylodynamic-analysis-of-ncov-2019-genomes-27-jan-2020/353.
4. Hill, V.; Rambaut, A., Phylodynamic analysis of SARS-CoV-2 | Update 2020-03-06. Virological: 2020.
5. Paraskevis, D.; Kostaki, E. G.; Magiorkinis, G.; Panayiotakopoulos, G.; Sourvinos, G.; Tsiodras, S., Full-genome evolutionary analysis of the novel corona virus (2019-nCoV) rejects the hypothesis of emergence as a result of a recent recombination event. Infect Genet Evol 2020, 79, 104212.
6. Liu, P.; Chen, W.; Chen, J.-P., Viral Metagenomics Revealed Sendai Virus and Coronavirus Infection of Malayan Pangolins (Manis javanica). Viruses 2019, 11 (11), 979.
7. Liu, P.; Jiang, J.-Z.; Wan, X.-F.; Hua, Y.; Wang, X.; Hou, F.; Chen, J.; Zou, J.; Chen, J., Are pangolins the intermediate host of the 2019 novel coronavirus (2019-nCoV) ? bioRxiv 2020, 2020.02.18.954628.
8. Lu, R.; Zhao, X.; Li, J.; Niu, P.; Yang, B.; Wu, H.; Wang, W.; Song, H.; Huang, B.; Zhu, N.; Bi, Y.; Ma, X.; Zhan, F.; Wang, L.; Hu, T.; Zhou, H.; Hu, Z.; Zhou, W.; Zhao, L.; Chen, J.; Meng, Y.; Wang, J.; Lin, Y.; Yuan, J.; Xie, Z.; Ma, J.; Liu, W. J.; Wang, D.; Xu, W.; Holmes, E. C.; Gao, G. F.; Wu, G.; Chen, W.; Shi, W.; Tan, W., Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. The Lancet 2020.
9. Su, Y. C.; Anderson, D. E.; Young, B. E.; Zhu, F.; Linster, M.; Kalimuddin, S.; Low, J. G.; Yan, Z.; Jayakumar, J.; Sun, L.; Yan, G. Z.; Mendenhall, I. H.; Leo, Y.-S.; Lye, D. C.; Wang, L.-F.; Smith, G. J., Discovery of a 382-nt deletion during the early evolution of SARS-CoV-2. bioRxiv 2020, 2020.03.11.987222.

Dr KK Aggarwal

President CMAAO, HCFI and Past National President IMA