Sterol Constituents of Sea Fan (Gorgonia mariae) as Potential Candidates of MPro Protein SARS-CoV-2 Inhibitor: in silico Study

Abstract

Ethnobotanically, sea fan was a group of gorgonian coral that have used the Maluku people as medicinal ingredients with secondary metabolites containing sterols, terpenoids, and alkaloids that have anti-inflammatory, anti-viral, anti-cancer, analgesic, gastroprotective, anti-bacterial, anti-cancer, and anti-fouling agents. However, the effectiveness of sterols as anti-viral SARS-CoV-2 has not been reported, so research was needed. The initial stage of targeting (SwissTargetPrediction), binding affinity (Autodock Tools 4.2), and amino acid interactions (Discovery Studio 2016 Client®). The route of administration, pharmacokinetic properties, and acute oral toxicity (LD₅₀) were predicted by Lipinski's rule of five, pre-ADMET, and ProTox-II. The results of target class obtained probability of 10.6% (4,24-dimethyl cholesta-7,22-dien-3ß-ol and 4,24-dimethyl-22-dehydro-cholestanol) and 11, 8% (dinosterol). Binding affinity (ΔG, kcal/mol and Ki, nM) potentially 4,24-dimethyl cholesta-7,22-dien-3ß-ol (-9.90; 55.13) > dinosterol (-9.77; 68.66) > 4,24-dimethyl-22-dehydro-cholestanol (-9.48; 113.33), respectively with the crucial amino acid, Asp187. The test compound has a log P value > 5, so solubility must be considered. Pre-ADMET showed an excellent disposition as a drug and was not mutagenic and carcinogenic. However, the distribution of plasma proteins and the dose of LD₅₀ need to be considered. Thus, sea fan sterols have potential as M^Pro protein inhibitors.