Association between COVID-19, diabetes mellitus type 1, and halitosis: A bioinformatics approach with therapeutic insights from seaweed metabolites

• Genes linking COVID-19, Diabetes Mellitus Type 1 (T1DM), and halitosis were identified using bioinformatics databases. • Shared pathways such as chemokine signaling and inflammatory response pathways were analyzed. • Marine algal metabolites from Bifurcaria bifurcata showed strong in silico binding to ACE2 and insulin receptor substrate proteins. COVID-19 and Diabetes Mellitus Type 1 (T1DM) exhibit a well-documented bidirectional relationship, underpinned by shared genetic and inflammatory mechanisms. Emerging clinical evidence suggests halitosis (oral malodor) may be a common manifestation in both conditions, linked to factors such as poor glycemic control, oral ACE2 expression, and dysbiosis. This study employed an integrated bioinformatics and computational approach to identify common genetic links between COVID-19, T1DM, and halitosis and to evaluate natural therapeutic candidates from marine algae. Gene database analysis identified shared genes (including DPP4, CRP, APOE, and TNNI3) and pathways, such as chemokine signaling and inflammatory response, connecting the three conditions. In silico docking of metabolites from Bifurcaria bifurcata revealed strong binding affinity to the ACE2 receptor and insulin receptor substrate. Critically, molecular dynamics simulations (100 ns) confirmed the exceptional stability of the leading metabolite complex, demonstrated by low RMSD/RMSF values and a constant binding site distance. Binding free energy calculations (MM/GBSA) further quantified robust binding affinity. These results not only elucidate a novel genetic and pathophysiological triad but also strongly suggest that seaweed-derived metabolites, supported by advanced dynamic and energetic profiling, represent promising therapeutic leads worthy of further experimental investigation.