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Gene variants of coagulation related proteins that interact with SARS-CoV-2

David Holcomb1, Aikaterini Alexaki1, Nancy Hernandez1

  • 1Center for Biologics Evaluation and Research, Office of Tissues and Advanced Therapies, Division of Plasma Protein Therapeutics, Food and Drug Administration, Silver Spring, Maryland, United States of America.

Plos Computational Biology
|March 17, 2021
PubMed

Insights

Investigating proteins linked to blood clots in COVID-19 (Coronavirus disease 2019) reveals genetic variants potentially worsening disease severity, especially in minority groups. Further research may improve understanding and treatment for severe COVID-19.

Area of Science:

  • Biochemistry
  • Genetics
  • Virology

Background:

  • Thrombosis is a serious complication of Coronavirus disease 2019 (COVID-19), linked to inflammation and poor outcomes.
  • Specific proteins involved in coagulation, including PABPC4, SERPING1, and VKORC1, are known to interact with SARS proteins.

Purpose of the Study:

  • To computationally examine interactions between coagulation-related proteins (PABPC4, SERPING1, VKORC1) and SARS-CoV-2 proteins.
  • To investigate the prevalence and potential impact of genetic variants in these proteins on COVID-19 severity.
  • To propose mechanisms for how these variants might influence disease and inform therapeutic strategies, particularly for disproportionately affected minority groups.

Main Methods:

  • Computational analysis of protein-protein interactions between human coagulation factors and SARS-CoV-2 proteins.
  • Detailed examination of VKORC1 binding to the SARS-CoV-2 ORF7a protein.
  • Population-based analysis of genetic variants in PABPC4, SERPING1, and VKORC1.
  • Proposing potential pathogenetic mechanisms for identified variants.

Main Results:

  • Confirmed interactions between PABPC4, SERPING1, and VKORC1 with SARS-CoV-2 proteins, with detailed analysis of VKORC1-ORF7a binding.
  • Identified population-specific variants in these coagulation-related proteins.
  • Observed that some prevalent variants are found in minority groups disproportionately affected by severe COVID-19.

Conclusions:

  • Genetic variants in coagulation-associated proteins may contribute to COVID-19 severity.
  • These variants, particularly those prevalent in minority populations, warrant further investigation for understanding disease pathogenesis.
  • This research could lead to more targeted therapeutic approaches for severe COVID-19.

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