Receptor Binding for the Entry Mechanisms of SARS-CoV-2 : Insights from the Original Strain and Emerging Variants
(2025) In Viruses 17(5).- 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... (More)
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.
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- author
- Mahdi, Mohamed ; Kiarie, Irene Wanjiru ; Mótyán, János András ; Hoffka, Gyula LU ; Al-Muffti, Aya Shamal ; Tóth, Attila and Tőzsér, József
- organization
- publishing date
- 2025-05
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- coronaviruses, COVID-19, receptor utilization, SARS-CoV-2, viral entry
- in
- Viruses
- volume
- 17
- issue
- 5
- article number
- 691
- publisher
- MDPI AG
- external identifiers
-
- pmid:40431702
- scopus:105006767942
- ISSN
- 1999-4915
- DOI
- 10.3390/v17050691
- language
- English
- LU publication?
- yes
- additional info
- Publisher Copyright: © 2025 by the authors.
- id
- d905b9a1-6b82-425b-912d-d9495d4b1817
- date added to LUP
- 2025-08-06 15:09:42
- date last changed
- 2025-08-07 03:00:02
@article{d905b9a1-6b82-425b-912d-d9495d4b1817,
abstract = {{<p>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.</p>}},
author = {{Mahdi, Mohamed and Kiarie, Irene Wanjiru and Mótyán, János András and Hoffka, Gyula and Al-Muffti, Aya Shamal and Tóth, Attila and Tőzsér, József}},
issn = {{1999-4915}},
keywords = {{coronaviruses; COVID-19; receptor utilization; SARS-CoV-2; viral entry}},
language = {{eng}},
number = {{5}},
publisher = {{MDPI AG}},
series = {{Viruses}},
title = {{Receptor Binding for the Entry Mechanisms of SARS-CoV-2 : Insights from the Original Strain and Emerging Variants}},
url = {{http://dx.doi.org/10.3390/v17050691}},
doi = {{10.3390/v17050691}},
volume = {{17}},
year = {{2025}},
}