Exploring the antimicrobial and antioxidative potential of Leucas aspera (Willd.) link: Phytochemical screening, molecular docking, and HR-LC/MS profiling against SARS-CoV-2 protein 3CLPro, Spike and RDB

• The study focuses on extracting the drug compounds from Leucas aspera and performed molecular docking studies against the SARS-CoV-2 receptor. • Metabolite profiling of the methanolic crude extract of L. aspera leaves, discovering 37 positive and 43 negative compounds • Our findings could serve as potential active molecules of L. aspera against the main protease and receptor binding domain protein of Sars-CoV-2. Leucas aspera (Willd.) Link, a member of the Lamiaceae family and commonly known as "Thumbai," is found throughout India and has been utilized in traditional Indian medicine to treat various ailments. This study entails methanolic extraction of Leucas aspera (Willd.) Link using a Soxhlet apparatus, followed by phytochemical screening and antioxidant activity assessment. The L. aspera methanolic leaf extract displayed a phenolic content of 100 µg/ml, consisting of 3.02 mg of gallic acid dry weight equivalents and a flavonoid content of 100 µg/ml with 3.35 mg quercetin equivalents per dry weight. The extract's free radical scavenging capabilities were at 150 µg/ml in DPPH, showing an 87% effectiveness compared to the standard ascorbic acid 49% inhibition capacity. The ABTS radical scavenging activity in 100 µg/ml extract measured 64.32%, phosphomolybdate assay indicated 86.89%, and hydroxide radical scavenging capacity showed 126.72%. Antibacterial activity was also assessed through agar well diffusion assays against Klebsiella pneumoniae, Salmonella typhi, Staphylococcus aureus , and Leucobacter sp ., Where K. pneumoniae exhibits the highest zone of inhibition. The methanolic crude extract of L. aspera was further using TLC, FT-IR and HR-LC/MS to identify functional groups and phytocompound present in the extract. HRLC-MS was used to conduct metabolite profiling of the methanolic crude extract of L. aspera leaves, discovering 37 positive and 43 negative compounds. To evaluate the ADMET properties and predict the drug-likeness of these 80 phytochemicals, an in silico analysis was performed. The results of this analysis revealed that only 19 of the compounds met the ADMET limitations and had suitable Log P values. Molecular docking of the 19 compounds against the SARS-CoV-2 main protease (3CL Pro ) protein (PDB ID: 6LU7) and spike protein receptor binding domain (SGp-RBD) protein (PDB ID: 2GHV) revealed Famprofazone and Loxtidine compounds having the highest binding affinity with LibDock scores of 105.53 and 116.70 respectively. Thus, our findings could serve as potential active molecules of L. aspera against this target protein. This study provides further proof of bioactive compounds produced by the L. aspera leaf extract.