A focused library of fifteen polycyclic marine batzelladine alkaloids were extensively explored for their binding affinities against the dimeric form of the Mpro of SARS-CoV-2 using a comprehensive package of computational tools involving MDock, MD and SARs studies. MDock simulations revealed that most of the tested compounds are demonstrating very promising binding scores particularly, batzelladines H-I (8-9) which displayed very close binding scores compared to the co-crystallized inhibitor (O6K, positive control). Indeed, the MD simulations showed an advantageous stability for almost of the investigated marine ligands at the (M pro ) binding site. Furthermore, a preliminary SAR study was accomplished to liaise between different structural features and how far they impacted the proposed activity. Those interesting findings figured out that such distinct molecular architectures are merited and could enlighten the development of promising antiviral leads for paving the COVID-19 pandemic. Moreover, considering the feasible total chemical syntheses for a notable number of these compounds or structurally related congeners could be encouraging for more in vitro /in vivo preclinical investigations for COVID-19 control.