Extensive analysis of the 39 lamellarins marine alkaloids under investigation, indicated that, the aromatic A-, E-, and F-rings are densely decorated either by hydroxy or methoxy groups. Additionally, in eight lamellarin derivatives, the A-, E-, and F-rings are also decorated by acetyl groups. Moreover, there are as further nine lamellarin derivatives that possess a sulfonyl group in the A-or E-ring. The 5,6-bond in ring D can be either saturated or unsaturated. In the SARS-CoV-2 Mpro activity of lamellarin derivatives, the existence of a hydroxyl group at position 14 of the ring F, that can exchange with position 13 in the same ring, appears to be essential. For the ten selected lamellarin derivatives for SARS-CoV-2 Mpro reported in Table , only lamellarin J ( ) does not follow this rule. Furthermore, the hydrophobic engagement by the F and A rings to the SARS-CoV-2 Mpro enzyme in reference amino acids such as Cys145 and His41, respectively, also seems very relevant.