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Receptor recognition by the novel coronavirus from Wuhan: an analysis based on decade-long structural studies of SARS coronavirus

Our take —

Using knowledge gleaned from a decade of studies on receptor binding in coronaviruses, this study finds that SARS-CoV-2 likely uses the ACE2 receptor to infect human cells and has favorable amino acid changes that may facilitate human-to-human viral transmission. The virus also shows affinity for other animal ACE2 proteins, which might act as intermediate hosts. However, experiments will be necessary to establish whether these animal species can be successfully infected.

Study design

Ecological, Modeling/Simulation, Other

Study population and setting

The study examines the molecular interactions between SARS-related coronaviruses and cells of their human and animal hosts. Specifically, the authors look at key changes in a special region of the coronavirus spike protein that binds to a receptor protein on cells of its animal and human hosts, the angiotensin-converting enzyme 2 (ACE2), and assess how changes might lead to an increased ability to bind and infect host cells.

Summary of Main Findings

Based on the genome of SARS-CoV-2 and existing knowledge of the interaction between SARS-related coronaviruses and human ACE2, it is likely that the novel virus is capable of infecting human cells by binding to ACE2. Several amino acid changes in SARS-CoV-2 provide favorable binding to sites on human ACE2, which suggests that there is some latent ability for human-to-human transmission of this novel virus. Comparison of ACE2 proteins in other animals indicates that SARS-CoV-2 may be capable of infecting pigs, ferrets, cats, and nonhuman primates, but not mice or rats, as intermediate hosts.

Study Strengths

Capitalizes on years of research on receptor binding in SARS-related coronaviruses collected since 2002, including artificial selection experiments to find the ideal amino acid residues for binding to human ACE2.

Limitations

Computer models of proteins can assess the affinity of the novel coronavirus to human ACE2 but cannot account for other factors that could affect the affinity of SARS-CoV-2 to human cells; these factors must be assessed with tissue culture or animal infection experiments. Likewise, analysis of ACE2 homologues in other animals does not establish that the novel virus will successfully infect these animals, only the potentiality. Experimental infections will be necessary to establish whether the virus can replicate in these intermediate hosts.

Value added

Assesses the favorable substitutions that increases the binding affinity of SARS-CoV-2 to human cells and identifies potential intermediate reservoir host species that may have been involved in the transition of the novel coronavirus from bats to humans.