Hydrogen Sulfide Inhibits TMPRSS2 in Human Airway Epithelial Cells: Implications for SARS-CoV-2 Infection

Area of Science:

• Virology and Respiratory Medicine
• Gasotransmitter Signaling
• Cellular and Molecular Biology

Background:

• The COVID-19 pandemic necessitates novel therapeutic and preventative strategies beyond vaccination.
• Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) utilizes angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2) for host cell entry, primarily in the respiratory system.
• Hydrogen sulfide (H2S), a gasotransmitter with known anti-inflammatory and anti-viral properties, is present in natural compounds and can be inhaled.

Purpose of the Study:

• To investigate the in vitro effects of H2S on TMPRSS2 and ACE2 expression in human airway epithelial cells.
• To assess the potential of H2S as a preventative measure against SARS-CoV-2 entry into respiratory cells.

Main Methods:

• Utilized human upper and lower airway epithelial cell lines and primary cells.
• Administered H2S donors to expose cells to varying concentrations of H2S.
• Quantified the expression levels of TMPRSS2 and ACE2 proteins using established laboratory techniques.

Main Results:

• Hydrogen sulfide (H2S) significantly downregulated the expression of TMPRSS2 in both respiratory cell lines and primary human airway epithelial cells.
• H2S treatment did not alter the expression levels of ACE2.
• These results were consistent across upper and lower airway epithelial cell models.

Conclusions:

• Inhalational exposure to H2S can reduce TMPRSS2 expression, a key factor for SARS-CoV-2 entry.
• Natural H2S sources may offer a protective mechanism by hindering viral entry into airway epithelial cells.
• This suggests a potential role for H2S in preventing SARS-CoV-2 spread within the respiratory tract.