The biological origin of COVID-19 is linked to three pathophysiological conditions: immunosuppression, viral infection, and inflammation. In the Philippines, nine alkaloids with potential antiviral and anti-inflammatory effects have been isolated from two plants, Uncaria perrottetii and Uncaria lanosa f. philippinensis, and their potential for COVID-19 therapy were investigated. Results showed that mitraphylline (L5) and uncarine B (L6) are two potential candidates as they exhibited the best binding energy score, lowest binding interaction energies, and lowest RMSD score. MMPBSA analysis indicated that complex binding energies of -128.295 ± 16.787 kJ/mol and -44.940 ± 10.918 for A2AR-5 and 3CL-6, suggesting that mitraphylline is a potential competitive antagonist in A2AR of caffeine, which is a known antagonist and inhibitor of the receptors, and uncarine B is a candidate inhibitor of 3CL protease. © 2022 ACM.