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A Fluorogenic Peptide Cleavage Assay to Screen for Proteolytic Activity: Applications for coronavirus spike protein activation
Published on: January 9, 2019
Human coronavirus spike protein-host receptor recognition
1School of Chemistry, University of Hyderabad, Hyderabad, 500046, India.
Abstract:
A variety of coronaviruses (CoVs) have infected humans and caused mild to severe respiratory diseases that could result in mortality. The human CoVs (HCoVs) belong to the genera of α- and β-CoVs that originate in rodents and bats and are transmitted to humans via zoonotic contacts. The binding of viral spike proteins to the host cell receptors is essential for mediating fusion of viral and host cell membranes to cause infection. The SARS-CoV-2 originated in bats (RaTG13 SARS-CoV) and is transmitted to humans via pangolins. The presence of 'PRRA' sequence motif in SARS-CoV-2 spike proteins from human, dog, cat, mink, tiger and lion suggests a common viral entry mechanism into host cells. In this review, we discuss structural features of HCoV spike proteins and recognition of host protein and carbohydrate receptors.
Insights
Human coronaviruses (HCoVs) cause respiratory illnesses. This review covers HCoV spike protein structures and host receptor interactions, crucial for understanding viral entry and infection mechanisms.
Area of Science:
- Virology
- Molecular Biology
- Infectious Diseases
Background:
- Human coronaviruses (HCoVs) are a significant cause of respiratory diseases, ranging from mild to severe and potentially fatal.
- HCoVs, including alpha- and beta-coronaviruses, originate in animals like rodents and bats and spread to humans through zoonotic transmission.
- Viral spike proteins are critical for initiating infection by binding to host cell receptors and facilitating membrane fusion.
Purpose of the Study:
- To review the structural characteristics of human coronavirus spike proteins.
- To explore the mechanisms by which HCoV spike proteins recognize and bind to host cell receptors (proteins and carbohydrates).
- To provide insights into the common viral entry mechanisms, exemplified by the 'PRRA' motif in SARS-CoV-2.
Main Methods:
- Literature review focusing on structural virology and molecular mechanisms of coronavirus infection.
- Analysis of published data on HCoV spike protein structures and their interactions with host receptors.
- Comparative analysis of spike protein features across different HCoV strains and hosts.
Main Results:
- HCoV spike proteins exhibit diverse structural features essential for host cell recognition and entry.
- The binding of spike proteins to specific host receptors (protein and carbohydrate) is a key determinant of viral tropism and infectivity.
- The conserved 'PRRA' sequence motif in SARS-CoV-2 spike proteins suggests a shared mechanism for host cell entry across various mammalian species.
Conclusions:
- Understanding HCoV spike protein structure and receptor interactions is vital for developing antiviral strategies.
- The zoonotic origin and interspecies transmission of HCoVs highlight the importance of One Health approaches.
- Further research into HCoV structural biology and host-pathogen interactions can elucidate viral pathogenesis and inform public health responses.
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