Bioinformatic assay reveal the potential mechanism of Guizhi-Shaoyao-Zhimu decoction against rheumatoid arthritis and mild-to-moderate COVID-19

Background and objective: Patients with rheumatoid arthritis (RA) are more susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) than healthy population, but there is still no therapeutic strategy available for RA patients with corona virus disease 2019 (COVID-19). Guizhi-Shaoyao-Zhimu decoction (GSZD), Chinese ancient experience decoction, has a significant effect on the treatment of Rheumatism and gout. To prevent RA patients with mild-to-moderate COVID-19 from developing into severe COVID-19, this study explored the potential possibility and mechanism of GSZD in the treatment of this population.

Methods: In this study, we used bioinformatic approaches to explore common pharmacological targets and signaling pathways between RA and mild-to-moderate COVID-19, and to assess the potential mechanisms of in the treatment of patients with both diseases. Beside, molecular docking was used to explore the molecular interactions between GSZD and SARS-CoV-2 related proteins.

Results: Results showed that 1183 common targets were found in mild-to-moderate COVID-19 and RA, of which TNF was the most critical target. The crosstalk signaling pathways of the two diseases focused on innate immunity and T cells pathways. In addition, GSZD intervened in RA and mild-to-moderate COVID-19 mainly by regulating inflammation-related signaling pathways and oxidative stress. Twenty hub compounds in GSZD exhibited good binding potential to SARS-CoV-2 spike (S) protein, 3C-like protease (3CLpro), RNA-dependent RNA polymerase (RdRp), papain-like protease (PLpro) and human angiotensin-converting enzyme 2 (ACE2), thereby intervening in viral infection, replication and transcription.

Conclusions: This finding provides a therapeutic option for RA patients against mild-to-moderate COVID-19, but further clinical validation is still needed.