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Publications

Journal Article Review Research Support, Non-U.S. Gov't Epublish

PubMed: 40431702 DOI: 10.3390/v17050691

Receptor Binding for the Entry Mechanisms of SARS-CoV-2: Insights from the Original Strain and Emerging Variants.

Viruses 17(5)

Authors: Mohamed Mahdi, Irene Wanjiru Kiarie, János András Mótyán, Gyula Hoffka, Aya Shamal Al-Muffti, Attila Tóth, József Tőzsér

Affiliations

  • Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary.
  • Department of Infectology, Faculty of Medicine, University of Debrecen, 4031 Debrecen, Hungary.
  • Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary. Doctoral School of Molecular Cellular and Immune Biology, University of Debrecen, 4032 Debrecen, Hungary.
  • Department of Chemistry, Lund University, Box 124, 221 00 Lund, Sweden.
  • Division of Clinical Physiology, Department of Cardiology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary.

Abstract

Since its emergence in late 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has continuously evolved, giving rise to multiple variants that have significantly altered the trajectory of the COVID-19 pandemic. These variants have resulted in multiple waves of the pandemic, exhibiting characteristic mutations in the spike (S) protein that may have affected receptor interaction, tissue tropism, and cell entry mechanisms. While the virus was shown to primarily utilize the angiotensin-converting enzyme 2 (ACE2) receptor and host proteases such as transmembrane serine protease 2 (TMPRSS2) for entry into host cells, alterations in the S protein have resulted in changes to receptor binding affinity and use of alternative receptors, potentially expanding the virus's ability to infect different cell types or tissues, contributing to shifts in clinical presentation. These changes have been linked to variations in disease severity, the emergence of new clinical manifestations, and altered transmission dynamics. In this paper, we overview the evolving receptor utilization strategies of SARS-CoV-2, focusing on how mutations in the S protein may have influenced viral entry mechanisms and clinical outcomes across the ongoing pandemic waves.

MeSH

Cells, Coronavirus, Sars-Cov-2, Virology, Viruses, Peptide Hydrolases, Pandemics, Severe Acute Respiratory Syndrome-Related Coronavirus, Tissues, Mutation, Virus Internalization

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