Pancreatin digestion of B-phycoerythrin from Porphyridium purpureum releases chromopeptides with inhibitory activity towards SARS-CoV-2 main protease

Abstract

Unique features of covalently attached tetrapyrrole chromophores give phycobiliproteins (PBPs) remarkable optical and bioactive properties with significant potential for application in the food industry, medicine, and biotechnology. This study investigated the potential of chromopeptides, released upon enzymatic digestion of major PBPs from cyanobacteria Limnospira platensis (C-Phycocyanin) and red microalgae Porphyridium purpureum (B-Phycoerythrin), to inhibit the main protease (M^pro) of SARS-CoV-2 virus. The digest obtained by pancreatin digestion of B-Phycoerythrin exhibits the highest inhibitory activity with estimated IC₅₀ values in the low micromolar range. Mass spectrometry was used to determine the sequence of RP-HPLC-purified chromopeptides, and small peptides (2–7 amino acid residues) were identified. The inhibitory activity of purified chromopeptides confirmed that chromopeptides are the major components in B-Phycoerythrin digest and are responsible for M^pro inhibition. The binding of chromopeptides to M^pro was evaluated using molecular docking, while molecular dynamics simulations were employed to propose a plausible mechanism of M^pro inhibition.