Potential PDE4B inhibitors as promising candidates against SARS-CoV-2 infection

Area of Science:

• Pharmacology
• Virology
• Medicinal Chemistry

Background:

• Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causes COVID-19, primarily impacting the pulmonary system, similar to COPD.
• Phosphodiesterase 4 (PDE4) inhibitors offer anti-inflammatory and bronchodilator effects by increasing cAMP levels.
• Existing PDE4 inhibitors like piclamilast have dose-limiting side effects (nausea, emesis).

Purpose of the Study:

• To investigate selective phosphodiesterase 4B (PDE4B) inhibition as a strategy against SARS-CoV-2.
• To identify potential drug candidates with reduced side effects for COVID-19 treatment.

Main Methods:

• Molecular docking studies were performed on 21 in-house compounds targeting the PDE4B catalytic site.
• Compounds were docked against the PDE4B active site, comparing their positions to the known inhibitor piclamilast.
• Drug-likeness prediction studies were conducted on the investigated compounds.

Main Results:

• The 21 in-house compounds were docked into the PDE4B catalytic site.
• Most compounds showed significant superposition with piclamilast, indicating potential binding affinity.
• Drug-likeness properties were evaluated for the screened compounds.

Conclusions:

• Selective PDE4B inhibition is a promising strategy for developing novel COVID-19 therapeutics.
• The studied compounds demonstrate potential as selective PDE4B inhibitors with improved side effect profiles.
• Further investigation into these compounds could lead to effective treatments for COVID-19.