A comprehensive analysis of the polyphenols constituents found in Thunbergia alata leaves using (UPLC-Triple TOF-MS/MS) and natural polyphenols' antiviral properties have motivated us to perform in silico binding affinity study of flavonoids and coumarins identified in T. alata leaves extract against different proteins of SARS-COV-2; (Mpro) main protease (PDB ID: 6LU7) and 2′-Omethyltransferase (PDB ID: 6wkq) using a cocrystalized ligands N3 and Sinefungin respectively. 30 compounds were tentatively identified in T. alata leaves extract by UPLC-Triple TOF-MS/MS and characterized as 8-phenolic acids; 12-flavonoids; 3-coumarins and remain compounds unidentified. In silico virtual screening of both flavonoids and coumarins as the most common classes of polyphenols; flavonoids have the best potential to act as COVID-19 Mpro & MTase inhibitors; especially Kaempferol-3-O-(6ˈˈˈ-p-coumaroyl)-glucoside; Comp. (17) which gave very best docking score{ -9.2 kcal/mol} (docking energy score of N3 -7.6 kcal/mol). It bind by nine hydrogen bonds (with TRY54, CYS145, GLN192, PHE140, LEU141, THR26, ARG188 and ASN142), and Pi-Sulfur interaction (with MET165), hydrophobic interactions via five Pi-Alkyl bond (with MET49, CYS145 and PRO168) and also scored energy binding -10.2 (docking energy score of Sinefungin -7.8 kcal/mol); formed H-bond with ASN6841, ASN6899, CYS6913, LYS6968, GLY6869, GLY6871, ASP6928, ASN6996 and TRY6930. Moreover, 17 binds with LYS6844, LYS6935, LEU6898 and CYS6913 via hydrophobic interactions. While coumarins in comparison with the current flavonoids had less energy binding score. However, further research is important to investigate their potential medicine value.