A focused list of 39 lamellarin marine pyrrole alkaloids (LAPs) were comprehensively investigated for their antiviral therapeutic potentialities against SARS-CoV-2 and Zika main proteases (Mpro) using a set of integrated modern computational tools including molecular docking (MDocking), molecular dynamic simulations (MDS) and Structure activity relationships (SARs). Particularly, [lamellarin H /lamellarin K ] and [lamellarin S / lamellarin Z ] were identified as promising antiviral hits for hunting SARS-CoV-2 and Zika main proteases (Mpro) respectively, based on their excellent ligand-protein energy scores and relevant binding affinities with (Mpro) pocket residues.