Along history, naturally occurring organic chemicals have always crucially recognized as a main source of valuable medications. Taking into consideration the SARS-CoV-2 and Zika main proteases (Mpro) as the re-production key element of the viral cycle and its main target, herein we report an intensive computer-aided virtual screening for a focused list of 39 marine lamellarins pyrrole alkaloids, against SARS-CoV-2 and Zika main proteases (Mpro) using a set of combined modern computational methodologies including molecular docking (MDock), molecule dynamic simulations (MDS) and structureactivity relationships (SARs) as well. Indeed, the molecular docking studies had revealed four promising marine alkaloids including [lamellarin H /lamellarin K ] and [lamellarin S / lamellarin Z ], according to their notable ligand-protein energy scores and relevant binding affinities with the SARS-CoV-2 and Zika (Mpro) pocket residues, respectively. Consequentially, these four chemical hits were further examined thermodynamically though investigating their MD simulations at 100 ns, where they showed prominent stability within the accommodated (Mpro) pockets. Moreover, in-deep SARs studies suggested the crucial roles of the rigid fused polycyclic ring system, particularly aromatic A-and F-rings, position of the phenolic -OH and -lactone functionalities as essential structural and pharmacophoric characteristics for an effective protein ligand interaction against SARS-CoV-2 and Zika Mpro, respectively. These motivating outcomes are greatly recommending further in vitro/vivo examinations regarding those marine derived compounds and their synthetic congeners, opening the gate to identify clinically useful antivirals based or bio-inspired from lamellarins pyrrole alkaloids (LPAs).