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Literature detail

Role of changes in SARS-CoV-2 spike protein in the interaction with the human ACE2 receptor: An <i>in silico</i> analysis.

Joseph Thomas Ortega1 Maria Luisa Serrano2 Flor Helene Pujol3 Hector Rafael Rangel3
Affiliations 3 institutions
  1. Department of Pharmacology and Cleveland Center for Membrane and Structural Biology, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA.
  2. Unidad de Química Medicinal, Facultad de Farmacia, Universidad Central de Venezuela, Caracas, Venezuela.
  3. Laboratorio de Virología Molecular, Centro de Microbiología y Biología Celular, Instituto Venezolano de Investigaciones Científicas, Caracas, Venezuela.
PMID 32210742 2020 EXCLI J eng epublish
PubMed DOI Browse context

Article

Publication summary

Many human viral diseases are a consequence of a zoonotic event. Some of the diseases caused by these zoonotic events have affected millions of people around the world, some of which have resulted in high rates of morbidity/mortality in humans. Changes in the viral proteins that function as ligands of the host receptor may promote the spillover between species. The most recent of these zoonotic events that have caused an ongoing epidemic of high magnitude is the Covid-19 epidemics caused by SARS-CoV-2. The aim of this study was to determine the mutation(s) in the sequence of the spike protein of the SARS-CoV-2 that might be favoring human to human transmission. An <i>in silico</i> approach was performed, and changes were detected in the S1 subunit of the receptor-binding domain of spike. The observed changes have significant effect on SARS-CoV-2 spike/ACE2 interaction and produce a reduction in the binding energy, compared to the one of the Bat-CoV to this receptor. The data presented in this study suggest a higher affinity of the SARS-Cov-2 spike protein to the human ACE2 receptor, compared to the one of Bat-CoV spike and ACE2. This could be the cause of the rapid viral spread of SARS-CoV-2 in humans.

ACE2 Coronavirus outbreak SARS-CoV-2 Spike

Structured evidence records

Evidence records

4 total
Receptor Usage 2 records
Receptor Usage Extraction confidence 0.95
Key finding

In silico analysis indicated that SARS-CoV-2 spike mutations enhance binding affinity to the human ACE2 receptor relative to Bat-CoV, suggesting improved receptor compatibility for human infection.

Virus
SARS-CoV-2
Location
Not specified
Supporting text

The observed changes have significant effect on SARS-CoV-2 spike/ACE2 interaction and produce a reduction in the binding energy, compared to the one of the Bat-CoV to this receptor. The data presented in this study suggest a higher affinity of the SARS-Cov-2 spike protein to the human ACE2 receptor, compared to the one of Bat-CoV spike and ACE2.

Method
in silico analysis
Receptors
ACE2 receptor
Receptor Usage Extraction confidence 0.90
Key finding

Comparison with Bat-CoV spike suggests lower binding energy for Bat-CoV spike to ACE2, indicating reduced receptor compatibility relative to SARS-CoV-2.

Location
Not specified
Supporting text

The observed changes have significant effect on SARS-CoV-2 spike/ACE2 interaction and produce a reduction in the binding energy, compared to the one of the Bat-CoV to this receptor.

Method
in silico analysis
Receptors
ACE2 receptor
Genomic Evolution 1 records
Genomic Evolution Extraction confidence 0.80
Key finding

In silico sequence comparison revealed mutations in the SARS-CoV-2 spike S1 receptor-binding domain relative to Bat-CoV, suggesting evolutionary adaptation for stronger binding to human ACE2.

Virus
SARS-CoV-2
Location
Not specified
Supporting text

The aim of this study was to determine the mutation(s) in the sequence of the spike protein of the SARS-CoV-2 that might be favoring human to human transmission. An in silico approach was performed, and changes were detected in the S1 subunit of the receptor-binding domain of spike. The observed changes have significant effect on SARS-CoV-2 spike/ACE2 interaction ... compared to the one of the Bat-CoV to this receptor.

Genes or proteins
spike; S1 subunit; receptor-binding domain
Analysis methods
in silico analysis; sequence comparison
Molecular Adaptation 1 records
Molecular Adaptation Extraction confidence 0.95
Key finding

SARS-CoV-2 spike protein shows changes in the receptor-binding domain that increase binding affinity to human ACE2 compared to Bat-CoV, indicating molecular adaptation promoting human infection.

Virus
SARS-CoV-2
Host
Not specified
Location
Not specified
Supporting text

Changes were detected in the S1 subunit of the receptor-binding domain of spike. The observed changes have significant effect on SARS-CoV-2 spike/ACE2 interaction, producing a reduction in the binding energy compared to Bat-CoV. The data suggest higher affinity of the SARS-CoV-2 spike protein to the human ACE2 receptor.

Genes or proteins
spike
Receptors
ACE2
Mechanism types
receptor_binding; cell_entry