Mechanism of Receptor Recognition in Coronavirus, 2nd Edition

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Animal Viruses".

Deadline for manuscript submissions: 30 September 2025 | Viewed by 1247

Special Issue Editor

Special Issue Information

Dear Colleagues,

Coronaviruses have continually demonstrated their remarkable adaptability and pathogenic potential, drawing intense global interest and underscoring the need for ongoing, in-depth research into the mechanisms of receptor recognition. Since the publication of the first volume of Mechanism of Receptor Recognition in Coronavirus, rapid developments have reshaped our understanding of coronavirus biology. Novel variants—most notably, the Omicron lineage and its subvariants—have emerged with significant mutations in the spike (S) protein, leading to altered virus–host interactions. These shifts present both immediate challenges and exciting research prospects in virology, immunology, therapeutic discovery, and vaccine development.

Building on the foundational insights gained from the first edition, this second volume expands the discussion around how coronaviruses exploit various receptors and co-receptors, and how spike protein mutations affect viral infectivity, host range, virulence, and immune evasion. Gaps in our knowledge remain, especially concerning the molecular signatures that drive tropism shifts and cross-species transmission—topics of pressing relevance given the expanding host range of coronaviruses. Equally pivotal are the continuing efforts to track and understand mutation-driven viral evolution. The accelerated appearance of mutations in the receptor-binding domain (RBD) has heightened concerns about potential immune escape, particularly in the face of widespread vaccination campaigns and the deployment of therapeutic antibodies. Addressing these concerns requires concerted efforts—from structural biologists employing high-resolution techniques to map virus–receptor interfaces, to clinical researchers monitoring vaccine efficacy and disease outcomes in real-time.

With this new volume, we aim to provide the scientific community with a comprehensive platform for sharing cutting-edge research and for fostering collaboration across disciplines. We invite contributions that not only dissect the molecular underpinnings of receptor recognition but also address the broader epidemiological and clinical ramifications of coronavirus evolution. By integrating multiple viewpoints—from structural biology and immunology to computational modeling and clinical research—this second edition aspires to drive ongoing progress in preventing, diagnosing, and treating coronavirus infections worldwide.

We look forward to your valuable submissions and to continuing the important dialogue initiated in the first volume.

Dr. Qibin Geng
Guest Editor

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Keywords

  • receptor recognition
  • spike protein adaptations
  • receptor-binding domain (RBD)
  • host range and zoonotic transmission
  • viral evolution and immune evasion
  • glycosylation and co-receptors
  • proteolytic activation
  • therapeutic and vaccine strategies
  • cross-species viral transmission
  • pandemic preparedness and surveillance

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Published Papers (2 papers)

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Review

17 pages, 2391 KiB  
Review
Evolution of Antiviral Drug Resistance in SARS-CoV-2
by Roy Dinata, Piyush Baindara and Santi M. Mandal
Viruses 2025, 17(5), 722; https://doi.org/10.3390/v17050722 - 18 May 2025
Viewed by 597
Abstract
The COVID-19 pandemic has had a significant impact and continues to alarm the entire world due to the rapid emergence of new variants, even after mass vaccinations. There is still an urgent need for new antivirals or strategies to combat the SARS-CoV-2 infections; [...] Read more.
The COVID-19 pandemic has had a significant impact and continues to alarm the entire world due to the rapid emergence of new variants, even after mass vaccinations. There is still an urgent need for new antivirals or strategies to combat the SARS-CoV-2 infections; however, we have success stories with nirmatrelvir. Drug repurposing and drug discovery may lead to a successful SARS-CoV-2 antiviral; however, rapid drug use may cause unexpected mutations and antiviral drug resistance. Conversely, novel variants of the SARS-CoV-2 can diminish the neutralizing efficacy of vaccines, thereby enhancing viral fitness and increasing the likelihood of drug resistance emergence. Additionally, the disposal of antivirals in wastewater also contributes to drug resistance. Overall, the present review summarizes the strategies and mechanisms involved in the development of drug resistance in SARS-CoV-2. Understanding the mechanism of antiviral resistance is crucial to mitigate the significant healthcare threat and to develop effective therapeutics against drug resistance. Full article
(This article belongs to the Special Issue Mechanism of Receptor Recognition in Coronavirus, 2nd Edition)
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26 pages, 1846 KiB  
Review
Receptor Binding for the Entry Mechanisms of SARS-CoV-2: Insights from the Original Strain and Emerging Variants
by Mohamed Mahdi, Irene Wanjiru Kiarie, János András Mótyán, Gyula Hoffka, Aya Shamal Al-Muffti, Attila Tóth and József Tőzsér
Viruses 2025, 17(5), 691; https://doi.org/10.3390/v17050691 - 10 May 2025
Viewed by 462
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 [...] Read 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. Full article
(This article belongs to the Special Issue Mechanism of Receptor Recognition in Coronavirus, 2nd Edition)
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