New Consensus pattern in Spike CoV-2: potential implications in coagulation process and cell-cell fusion

Area of Science:

• Virology
• Molecular Biology
• Hematology

Background:

• Coagulopathy and syncytial formation are significant complications of SARS-CoV-2 infection.
• The precise molecular mechanisms driving these COVID-19 pathologies remain unclear.

Purpose of the Study:

• To identify molecular patterns within the SARS-CoV-2 Spike (S) glycoprotein.
• To investigate potential functional similarities between the S protein and host proteins involved in coagulation and cell-cell interactions.

Main Methods:

• Bioinformatic analysis of the SARS-CoV-2 Spike protein's cytoplasmic domain.
• Comparison of identified patterns against the UniProt protein database.
• Identification of homologous patterns in human and bat coronavirus proteins and host factors.

Main Results:

• A specific consensus pattern was identified in the SARS-CoV-2 S protein, present in a small fraction of known proteins.
• This pattern was also found in S proteins of human and bat coronaviruses.
• Homologous patterns were detected in human proteins crucial for coagulation (e.g., von Willebrand factor, coagulation factor X) and cell fate regulation (e.g., fibronectin, Notch), often featuring EGF-like domains.

Conclusions:

• The identified pattern suggests functional similarities between the SARS-CoV-2 S protein and host proteins involved in coagulation and cell-cell fusion.
• This finding offers a potential molecular explanation for the coagulopathy and syncytial formation observed in COVID-19 patients.
• The SARS-CoV-2 S protein may directly participate in the pathogenesis of these COVID-19 complications.