Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding
Lu R, Zhao X, Li J, et al. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet. 2020;395(10224):565–574. doi:10.1016/S0140-6736(20)30251-8
Review written by:
Olivia Balderes, edited by Sarah Dugger
Green - Lancet publication, research support provided by multiple governmental agencies and Universities in China
Nine individuals with viral pneumonia of unknown cause (bacterial and common viral causes were ruled out using three panels) provided bronchoalveolar
lavage fluids or throat swab samples: eight of the individuals had visited the Huanan Seafood Market, and the ninth had stayed in a hotel close to the market, all presenting with symptoms in late December 2019 (Dec. 22-29). All samples were collected between Dec. 26 and Jan. 7. The virus was isolated from ten samples by inoculating pathogen-free HAE, and sent to BGI for RNA sequencing. Six of the nine viral RNA samples were sent to the CDC for Whole Genome Sequencing (combination Sanger, Illumnina, and Oxford, to ensure complete coverage).
Contigs identified in the samples indicated a close relation with bat-SL-CoVZC45 (87 .99% sequence identity), which was subsequently selected as the reference genome for the next gen sequencing. In total 8 complete genomes, and two partial genomes were generated. The complete genome sequences had ~99.98% sequence identity, which indicated a recent introduction to humans, as well as a rapid spread amongst (short time period from T0 infection) those infected. 2019-nCoV was shown to be distinct from SARS-CoV in the RNA-dependent RNA polymerase (RdRp) gene making it distinct phylogenetically. Notably, however, SARS-CoV and 2019-nCoV shared a highly conserved region of the envelope spike protein S2 domain, which dictates host receptor binding. Based on prior knowledge of SARS-CoV, the researchers propose that 2019-nCoV may use the human ACE2 receptor as a host receptor.
1) 2019-nCov originated from a single source in a short period of time, and was detected quickly (as indicated by high relative sequence identity)
2) Phylogenetic analysis revealed that 2019-nCoV is a new betacoronavirus from the Sarbecovirus subgenus.
3) 2019-nCoV was likely initially hosted in bats, and transmitted to humans via a third animal host at the Wuhan Market (as indicated by WGS and phylogeny) though mode of transmission was unknown for 1 of the 9 patients, who had not visited the market
4) 2019-nCoV may use ACE2 as a host receptor in humans
Small & early sample: characterization of the virus in a relatively homogenous population, before mass viral spread (Dec 2019); acknowledged.
ACE2 binding has been confirmed by later studies
Uniformity in methods used to rule out other viral and bacterial causes of Pneumonia, questionable. (5 samples processed by CDC, 4 processed by BGI)
2 samples had only partial sequencing, no explanation as to why; still considered in citations of virus’ genomic sequence identity.