Abstract
COVID-19 persists globally with profound social and economic consequences, and its complex interplay with other diseases makes it a syndemic. Rheumatoid arthritis (RA), a chronic autoimmune disorder, has shown increased incidence during the pandemic, with patients displaying higher susceptibility to COVID-19. This overlap prompted the hypothesis of 'COVID-19-associated rheumatoid arthritis (CARA)'. The present study explores phytocompounds with anti-inflammatory and immunomodulatory properties as potential CARA therapeutics. Compounds from Prosopis glandulosa and Symplocos racemosa, both used in traditional medicine, were evaluated through molecular docking and simulation studies. Six inflammatory targets relevant to RA and COVID-19 -interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), granulocyte-macrophage colony-stimulating factor (GM-CSF), human leukocyte antigen DR4 (HLA-DR4), signal transducer and activator of transcription 4 (STAT4), and peptidyl arginine deiminase 4 (PAD4) were selected. Among the tested ligands, salidroside showed the strongest binding affinity, with energies of - 8.20 kcal/mol (IL-6), - 7.67 kcal/mol (TNF-α), - 8.53 kcal/mol (GM-CSF), - 8.80 kcal/mol (HLA-DR4), - 8.18 kcal/mol (STAT4), and - 7.91 kcal/mol (PAD4), indicating stable interactions. These findings suggest salidroside could modulate key inflammatory pathways and potentially reduce cytokine storms in COVID-19 patients. Existing RA and COVID-19 treatments often cause immunosuppression, increasing vulnerability to opportunistic infections (Datta et al in J Biomol Struct Dyn 41(8):3281-3294, 2022). Immunomodulatory phytocompounds like salidroside may offer safer, targeted alternatives without compromising immune defenses. However, this study is based on in silico analyses, and warrants in vitro and in vivo validation. Nevertheless, present work may represent an important step towards novel therapeutic strategies for COVID-19 Associated Rheumatoid Arthritis (CARA).