<![CDATA[Inflammation, pain, and fever are physiological responses commonly managed with nonsteroidal anti-inflammatory drugs (NSAIDs), which act by inhibiting cyclooxygenase (COX). Cyanobacteria are a rich source of structurally diverse secondary metabolites with reported pharmacological activity, yet their potential as COX inhibitors has been little explored computationally. This study evaluated cyanobacterial secondary metabolites as candidate COX-1 and COX-2 inhibitors through an integrated in silico workflow combining Lipinski screening, molecular docking, residue interaction analysis, and ADMET prediction. Of 707 metabolites retrieved from the Comprehensive Marine Natural Products Database, 153 satisfied Lipinski's rule of five and were docked against COX-1 (PDB 4O1Z) and COX-2 (PDB 5IKR) using AutoDock Vina. Re-docking reproduced the co-crystallised ligand poses with root mean square deviation values of 1.04 Å for COX-1 and 1.87 Å for COX-2, confirming that the docking parameters were valid. The metabolites showed binding affinities comparable to several positive controls for COX-1 but lower than the reference inhibitors for COX-2. On the combined basis of binding affinity, binding pose, residue interactions, and ADMET, kalkipyrone, ypaoamide C, and dehydroabietic acid were prioritised as candidates. Kalkipyrone reproduced the catalytic Ser530 hydrogen bond within COX-2, and all three complied with Lipinski's rule of five and showed predicted profiles compatible with oral administration. These findings are computational predictions and require confirmation through molecular dynamics simulation and in vitro and in vivo assays.]]>
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