Analysis of the molecular mechanism of Pudilan (PDL) treatment for COVID-19 by network pharmacology tools

Graphical abstract
Highlights • Pudilan (PDL) was proven to be useful in the treatment of 2019 novel coronavirus disease (COVID-19). • Pudilan (PDL) might inhibit the cytokine storm in 2019 novel coronavirus disease (COVID-19) by affecting Interleukin-1β (IL-1β) and related proteins. • Pudilan (PDL) might prevent the entry of SARS-CoV-2 into cells by affecting angiotensin I converting enzyme 2 (ACE2). • Pudilan (PDL) might also moderate human immune system with traditional Chinese medicine theory.
Background Pudilan (PDL), a four-herb prescription with the traditional function of heat-clearing and detoxifying, has been clinically used as an anti-SARS-CoV-2 infectory agent in China. PDL might also have therapeutic potentials for COVID-19 while the underlying mechanisms remain to be clarified. Methods We used network pharmacology analysis and selected 68 co-targeted genes/proteins as targets of both PDL and COVID-19. These co-targeted genes/proteins were predicted by SwissDock Server for their high-precision docking simulation, and analyzed by STRING for proteins to protein interaction (PPI), pathway and GO (gene ontology) enrichment. The therapeutic effect for PDL treatment on COVID-19 was validated by the TCMATCOV (TCM Anti COVID-19) platform. Results PDL might prevent the entrance of SARS-CoV-2 entry into cells by blocking the angiotensin-converting enzyme 2 (ACE2). It might inhibit the cytokine storm by affecting C-reactive protein (CRP), interferon-γ (IFN-γ), interleukin- 6 (IL-6), interleukin- 10 (IL-10), tumor necrosis factor (TNF), epidermal growth factor receptor (EGFR), C-C motif chemokine ligand 5 (CCL5), transforming growth factor-β1 (TGFβ1), and other proteins. PDL might moderate the immune system to shorten the course of the disease, delay disease progression, and reduce the mortality rate. Conclusion PDL might have a therapeutic effect on COVID-19 through three aspects, including the moderate immune system, anti-inflammation, and anti-virus entry into cells.