A recent publication in the Physiological Reports discusses the importance of the mucous layer protein “mucin” as a potential tool to predict coronavirus susceptibility.
SARS-CoV-2 pathology
SARS-CoV-2 is considered to be a phylogenetic sister to the SARS virus because the two share approximately 80% sequence similarity.
In order to enter into cells, corona viruses bind to a cell surface receptor for attachment, subsequently entering the endosomes, and then fusion of the viral and lysosomal membranes occur.
Similar to the SARSCoV, the entry of SARS-CoV-2 into cells occurs by binding of the receptor binding domain (RBD) of the viral spike (S) protein, that is a part of the viral envelope, to the angiotensin converting enzyme 2 (ACE2) receptors present on various human tissues, including but not limited to the heart, blood vessels, gut (intestinal epithelial cells), lung, kidney, testis and brain.
The RBD keeps switching between two positions, standing-up for receptor binding and lying-down to evade immune response.
Role of Mucins in infection
In order to survive the external environment, most mammals, including humans use complex molecules as a protective barrier called mucins that make up a thick layer of mucus. The mucus layer acts as a first line of defense and is part of our innate immunity.
Mucins are mainly produced by surface goblet cells and glandular epithelial cells that are connected to other parts of the innate and adaptive immune systems. Mucins are heavy transmembrane and secreted heterodimeric glycoproteins, and their degree of glycosylation determines their protective function.
Mucins are present on almost all epithelial cells lining the respiratory, gastrointestinal and reproductive organs. Mucins are mainly made up of O-glycosylated repeats which bind water and give them their characteristic gel-like properties.
Connection of Mucins to COVID-19
Other than binding to their specific receptors, viruses utilize the transmembrane glycoproteins (including mucins) to enter into epithelial cells. Therefore, glycosylation profiles of the mucins in patients will be a useful tool in finding a pattern to predict infection susceptibility and disease progression.
The outer layer of the airway epithelial cells contains gel-forming mucins (MUC5AC and MUC5B) while the inner layer consists of membrane tethered mucins (MUC1, MUC4 and MUC16) that are occasionally shed from the apical cell surface.
During infection of the airways, these mucins act as a protective barrier against pathogens. Mucins also serve as a binding site for various pathogens, and might help entry and/or exit of SARS-CoV-2.
Differential and specific glycosylation patterns on certain mucins may restrict/enhance binding of virus to its respective receptor on epithelial cells by various mechanisms including steric hindrance.
- The research hypothesizes that the glycome signature and signature of shed mucins in circulation from infected lung or respiratory tract epithelial cells may correlate with the outcome of viral infection and disease progression.
- Researchers also hypothesized that the pattern of glycosylation of the above-mentioned mucins from the epithelial cells may help understand the differential internalization of the virus.
Conclusion
The purpose of the research was to encourage more research on mucins and their roles in the pathophysiology of COVID-19 patients, which may in future help predict disease susceptibility, disease progression and response to therapy.
Understanding how the mucin signature distinguishes an asymptomatic spreader from a symptomatic spreader or a highly susceptible individual to one with low susceptibility will be helpful to determine the population that is at high-risk. This type of analysis will also
consider the disparity that we see in different human races.
The analyses could also be extended to study susceptibility in other animal species, for
example, dogs that are being suspected to have contracted the disease from their owners.
This identification will aid in making better policies for new work-related quarantine measures for the vulnerable people, thus saving time, money and effort in combating the COVID-19 pandemic and other future global outbreaks.
Did you subscribe to our daily newsletter?
It’s Free! Click here to Subscribe!
Source: The Physiological Society
