OmniVira

Phylogenetic Analysis and Structural Modeling of SARS-CoV-2 Spike Protein Reveals an Evolutionary Distinct and Proteolytically Sensitive Activation Loop.

Javier A Jaimes1 Nicole M André1 Joshua S Chappie2 Jean K Millet3 Gary R Whittaker4,5
Affiliations 5 institutions
  1. Department of Microbiology & Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
  2. Department of Molecular Medicine, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
  3. Université Paris-Saclay, INRAE, UVSQ, Virologie et Immunologie Moléculaires, 78350 Jouy-en-Josas, France. Electronic address: [email protected].
  4. Department of Microbiology & Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA
  5. Master of Public Health Program, Cornell University, Ithaca, NY 14853, USA. Electronic address: [email protected].
PMID32320687 DOI10.1016/j.jmb.2020.04.009 Year2020 Journal Journal of molecular biology J Mol Biol Languageeng Statusppublish

Abstract

The 2019 novel coronavirus (2019-nCoV/SARS-CoV-2) originally arose as part of a major outbreak of respiratory disease centered on Hubei province, China. It is now a global pandemic and is a major public health concern. Taxonomically, SARS-CoV-2 was shown to be a Betacoronavirus (lineage B) closely related to SARS-CoV and SARS-related bat coronaviruses, and it has been reported to share a common receptor with SARS-CoV (ACE-2). Subsequently, betacoronaviruses from pangolins were identified as close relatives to SARS-CoV-2. Here, we perform structural modeling of the SARS-CoV-2 spike glycoprotein. Our data provide support for the similar receptor utilization between SARS-CoV-2 and SARS-CoV, despite a relatively low amino acid similarity in the receptor binding module. Compared to SARS-CoV and all other coronaviruses in Betacoronavirus lineage B, we identify an extended structural loop containing basic amino acids at the interface of the receptor binding (S1) and fusion (S2) domains. We suggest this loop confers fusion activation and entry properties more in line with betacoronaviruses in lineages A and C, and be a key component in the evolution of SARS-CoV-2 with this structural loop affecting virus stability and transmission.

Supporting text Virus Host Location
cleavage sites 1 coronavirus 195 COVID-19 467 SARS-CoV-2 550 spike protein 32 Amino Acid Sequence 128 Animals 1948 Betacoronavirus 78 Chiroptera 371 Coronavirus Infections 171 COVID-19 425 Eutheria 9 Humans 1440 Models, Molecular 99 Pandemics 108 Phylogeny 805 Pneumonia, Viral 42 Proteolysis 5 SARS-CoV-2 453 Sequence Alignment 51 Severe acute respiratory syndrome-related coronavirus 78 Spike Glycoprotein, Coronavirus 274 spike protein, SARS-CoV-2 157

Evidence records

1 total
Functional Mechanism
1 records · 1 evidence types
Evidence type Receptor Usage
1 records
OVE3746 Receptor Usage
Key finding

Structural modeling indicates that SARS-CoV-2 and SARS-CoV both utilize the ACE-2 receptor for cell entry, showing similar receptor usage despite low amino acid similarity in the binding module.

Virus
Severe acute respiratory syndrome coronavirus 2 Severe Acute Respiratory Syndrome Coronavirus
Host
Not specified
Location
Not specified
Supporting text

Taxonomically, SARS-CoV-2 was shown to be a Betacoronavirus (lineage B) closely related to SARS-CoV and SARS-related bat coronaviruses, and it has been reported to share a common receptor with SARS-CoV (ACE-2). Our data provide support for the similar receptor utilization between SARS-CoV-2 and SARS-CoV, despite a relatively low amino acid similarity in the receptor binding module.

Method
structural modeling | structural comparison of spike glycoprotein
Receptors
ACE-2