The derivatives with the lowest G calculated, i.e., the most promising derivatives, are lamellarin K Intriguingly, the 14-OH functionality of lamellarin derivatives, found in ring -F apparently participates in potential hydrogen-bonding interactions with the side chains of Gly143 and Ser144 of the SARS-CoV-2 Mpro enzyme as can be seen in lamellarin H and lamellarin K (17), Figure . Also very relevant are the hydrophobic interactions of the ring F with the Cys145 residue of the enzyme. Other relevant hydrophobic interaction is between the ring A and His41 residue of the enzyme. The double bond between C5 and C6 in ring B appear to be not essential for activity against SARS-CoV-2 Mpro, the lamellarin H ( ) has the double bond however the lamellarin K (17) does not have.