Bacterial Proteases as Potentially Exploitable Modulators of SARS-CoV-2 Infection: Logic from the Literature,...

Area of Science:

• Microbiology
• Virology
• Bioinformatics

Background:

• The COVID-19 pandemic revealed complex vulnerability factors beyond genetics and exposure.
• Nasal microbiome profiles are increasingly recognized for their role in differential infection rates among various demographics.
• Understanding these microbial influences is crucial for explaining varied COVID-19 susceptibility.

Purpose of the Study:

• To investigate the protective role of specific nasal commensal bacteria against SARS-CoV-2 infection.
• To explore the hypothesis that bacterial proteases can interfere with the SARS-CoV-2 spike protein's functionalization.
• To link nasal microbiome composition to COVID-19 resistance in different populations.

Main Methods:

• Literature review and analysis of existing microbiome profiling data.
• Bioinformatic analysis to identify bacterial proteases with homology to human enzymes.
• Molecular simulations to model protease-spike protein interactions.

Main Results:

• Elevated levels of Moraxella bacteria were observed in COVID-19 resistant groups (e.g., adolescents, diverse diets).
• Reduced Moraxella presence correlated with increased vulnerability (e.g., elderly, restricted diets).
• Moraxella species were found to express proteases homologous to human TMPRSS2, capable of cleaving the SARS-CoV-2 spike protein.

Conclusions:

• The nasal bacterium Moraxella may confer resistance to SARS-CoV-2 infection.
• Bacterial proteases, particularly from Moraxella, could inhibit viral entry by interfering with spike protein priming.
• Nasal microbiome composition is a significant factor in COVID-19 susceptibility and resistance.