Potential antiviral activity of eleutherine, isoeleutherine, eleuthinone and elecanacine compounds in Eleutherine palmifolia (L.) Merr against NSP3 SARS-COV-2: In silico study

Abstract

Eleutherine, isoeleutherine, eleuthinone and elecanacine are secondary metabolites of Dayak onion (Eleutherine palmifolia (L.) Merr) belonging to the naphtoquinone group and considered to have antiviral activity by inhibiting HIV replication. These considerations were used in this study using the Non-structural protein 3 (NSP3) in SARS-CoV-2 which plays a role in virus replication. This study aims to predict the antiviral activity, physicochemical properties and toxicity. Antiviral activity predictions were reviewed based on the interaction of the ligand with the NSP3 receptor (PDB ID: 7JIT) using Molegro Virtual Docker 6.0. Prediction of physicochemical properties refers to the Lipinski Ro5 and parameters of TPSA using swissADME. Toxicity prediction based on LD50 classification and AMES toxicity, hapatotoxicity, skin sensitization parameters using ProTox-II and pkCSM. The results showed that all the compounds in the study had inhibitory activity in terms of Rerank Score (RS) which represents the form of bound energy and were compared with Ribavirin as the comparator drug. The RS (Kcal/mol) for eleuthinone is -102.853, isoeleutherine -108.493, eleuthinone -108.005 and elecanacine -104.640. The RS of all compounds was lower than Ribavirin (-94.195) indicating higher affinity than Ribavirin. All the compounds in this study matched the Lipinski’s Ro5 and TPSA parameters with LD50 in toxicity class IV and were predicted to be safe, except for elecanacine which was predicted to be mutagenic and eleuthinone which was predicted to be hepatotoxic. So that, overall eleutherine and isoeleutherine compounds can be recommended as candidates for SARS-CoV-2 antiviral compounds.