Metabologenomics approach to the discovery of novel compounds from sp. GMR22 as anti-SARS-CoV-2 drugs.

COVID-19 is spreading rapidly yet there is no clinically proven drug available now. Soil-derived sp. GMR22 has a large genome size (11.4 Mbp) and a huge BGCs (Biosynthetic Gene Clusters) encoding secondary metabolites. This bacterium is a potential source for producing a wide variety of compounds which are able to block SARS-CoV-2, the causative agent of COVID-19. This study aimed to predict the secondary metabolites of sp. GMR22 and to evaluate the ability as SARS-CoV-2 inhibitor. The AntiSMASH 5.0 was used for genome mining analysis and targeted liquid chromatography-high resolution mass spectrometry (LC-HRMS) was used for metabolite analysis. In silico molecular docking was performed on important target proteins of SARS-CoV-2 i.e., spike protein (PDB ID: 6LXT), Receptor Binding Domain (RBD)-ACE2 (Angiotensin-Converting Enzyme 2) (PDB ID: 6VW1), 3CLpro (3-chymotrypsin-like protease) (PDB ID: 6M2N), and RdRp (RNA-dependent RNA polymerase) (PDB ID: 6M71). Two compounds from GMR22 extract, echoside A and echoside B were confirmed by targeted LC-HRMS and potential as SARS-CoV-2 inhibitor. Echoside A and echoside B showed higher docking score than remdesivir as COVID-19 drug on four target proteins, i.e., spike protein (-7.9 kcal/mol and -7.8 kcal/mol), RBD-ACE2 (-7.5 kcal/mol and -8.2 kcal/mol), 3CLpro (-8.4 kcal/mol and -9.4 kcal/mol) and RdRp (-7.3 kcal/mol and -8.0 kcal/mol). A combination of genome mining and metabolomic approaches can be used as integrated strategy to elucidate the potential of GMR22 as a resource in the discovery of anti-COVID -19 compound.