COVID-19: Epidemiology, Evolution, and Cross-Disciplinary Perspectives

Abstract

The recent outbreak of COVID-19 in Wuhan turned into a public health emergency of international concern. With no antiviral drugs nor vaccines, and the presence of carriers without obvious symptoms, traditional public health intervention measures are significantly less effective. Here, we report the epidemiological and virological characteristics of the COVID-19 outbreak. Originated in bats, 2019-nCoV/ severe acute respiratory syndrome coronavirus (SARS-CoV)-2 likely experienced adaptive evolution in intermediate hosts before transfer to humans at a concentrated source of transmission. Similarities of receptor sequence binding to 2019-nCoV between humans and animals suggest a low species barrier for transmission of the virus to farm animals. We propose, based on the One Health model, that veterinarians and animal specialists should be involved in a cross-disciplinary collaboration in the fight against this epidemic.

Figure 1

Spreading of the 2019-nCoV Epidemic. (A) Timeline of events during the 2019-nCoV epidemic. (B) Human confirmed cases of 2019-nCoV infection in China. (C) Human confirmed cases of 2019-nCoV infection in the world (Last update on 24:00 UTC+8, 20 February 2020). Abbreviations: CDC, Centers for Disease Control; ICTV, International Committee on Taxonomy of Viruses.

Figure 2

Structure of the 2019-nCoV Genome. (A) Recombination analysis of 2019-nCoV. A rescaled structure of the 2019-nCoV genome (top) and similarity recombination analysis with reference sequences using Simplot v3.5.1 (accession number BetaCoV/Wuhan/WIV02/2019|EPI_ISL_402127 EPI_ISL_402131, KJ473816, DQ071615, DQ412043, GQ153543, AY394995, KF569996, MG772933, MG772934). Sequences were separated based on potential recombination breakpoint on nucleotides 13 522 and 23 686. Maximum likelihood (ML) phylogenetic trees inferred for the pink and purple regions confirm different topologies and recombination. (B) ML tree of 2019-nCoV spike protein gene. The ML tree was reconstructed using the general time reversible substitution model with gamma distributed rate heterogeneity and 1000 bootstraps using RAxML (v4.8.10).

Figure 3

Structure of Spike Protein (S) Before and After Membrane Fusion. (A) Structure of the trimeric ectodomain of S from 2019-nCoV. The S2 subunit in one monomer is shown in green, the N terminal domain (NTD) of S2 in magenta, and the C terminal domain (CTD) of S2 in blue. The CTD is in the ‘up-conformation’, exposing the binding domain for the angiotensin-converting enzyme 2 (ACE2) receptor (cyan). The S1/S2 and S2′ cleavage sites are indicated in red. The figure was created with Pymol from Protein Data Bank (PDB) file 6VSB. (B) Structure of the heptad repeat (HR) domains of S from severe acute respiratory syndrome coronavirus (SARS-CoV). Heptad repeat region 1 (HR1) is labeled green and repeat region 2 (HR2) in blue. Formation of this six-helix bundle is supposed to drive membrane fusion. The figure was created with Pymol from PDB file 1ZV8. (C) Structure of the HR1 of S from SARS-CoV (green) bound to the pan-coronavirus peptide inhibitor EK1 (blue). The amino acids in S essential for binding to EK1 are shown as magenta sticks in one helix. The amino acids in S from 2019-nCoV not conserved in S from SARS-CoV are shown as red sticks. Since the nonconserved amino acids are apparently not required for binding to EK1, the fusion inhibitor is likely to prevent cell entry of 2019-nCoV. The figure was created with Pymol from PDB file 5ZVM. Abbreviations: RBD, receptor-binding domain.

Figure 4

Spike Protein (S) and Its Receptor. (A) Structure of the receptor-binding domain of S from 2019-nCoV (green) bound to human angiotensin-converting enzyme 2 (ACE2) (blue). Most amino acids involved in binding are highlighted as magenta (S) and cyan (ACE2) sticks. Asparagine (N) that are N-glycosylation sites (motif N-X-S/T) in human ACE2 are shown as orange sticks. Amino acids in human ACE2 that are involved in binding, but encode a potential N-glycosylation site in ACE2 from other species, are shown as red sticks. The dotted line indicates the salt bridge between D30 and K417 (generated with Pymol from Protein Data Bank file6VSB). (B) Amino acid exchanges between human ACE2 and pig ACE2. Amino acid exchanges in ACE2 from pig compared with human ACE2 are highlighted in red. The exchange N90T destroys the N-glycosylation site in human ACE2. (C) Amino acid exchanges between human ACE2 and cattle ACE2. Amino acid exchanges in ACE2 from cattle compared with human ACE2 are highlighted in red. The exchange N322Y destroys the N-glycosylation site in human ACE2. ACE2 from sheep exhibits identical amino acid exchanges. (D) Amino acid exchanges between human and cat ACE2. Amino acid exchanges in ACE2 from cat compared with human ACE2 are highlighted in red. All relevant glycosylation sites in human ACE2 are conserved.