The COVID-19 pandemic in Egypt is a part of the worldwide global crisis of coronavirus 2 (SARS-CoV-2). The contagious life-threatening condition causes acute respiratory syndrome. The present study aimed to assess the compounds identified by LC-MS of the methanolic leaves extracts from three conifers trees cultivated in Egypt (
Araucaria bidwillii, Araucaria. cunninghamii
and
Araucaria heterophylla
) via docking technique as potential inhibitor of COVID-19 virus on multiple targets; viral main protease (M
pro
, 6LU7), non-structural protein-16 which is a methyl transferase (nsp16, 6W4H) and RNA dependent RNA polymerase (nsp12, 7BV2). Among the three targets, nsp16 was the best target recognized by the tested compounds as can be deduced from docking studies. Moreover, the methanolic extract of
A. cunninghamii
showed the highest radical-scavenging activity using (DPPH test) with 53.7 µg/mL comparable to ascorbic acid with IC
50
= 46 µg/mL The anti-inflammatory potential carried using enzyme linked immunoassay showed the highest activity for
A. cunninghamii
and
A. bidwillii
followed by
A. heterophylla
with IC
50
= 23.20 ± 1.17 µg/mL, 82.83 ± 3.21 µg/mL and 221.13 ± 6.7 µg/mL, respectively (Celecoxib was used as a standard drug with IC
50
= 141.92 ± 4.52 µg/mL). Moreover, a molecular docking study was carried for the LC-MS annotated metabolites to validate their anti-inflammatory inhibitory effect using Celecoxib as a reference compound and showed a high docking score (−7.7 kcal/mol) for Octadecyl (
E
)
P
-coumarate and (−7.3 kcal/mol) for secoisolariciresinol rhamnoside.
Communicated by Ramaswamy H. Sarma