ABSTRACT
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections have triggered a recent pandemic of respiratory disease and affected almost every country all over the world. A large amount of natural bioactive compounds are under clinical investigation for various diseases. In particular, marine natural compounds are gaining more attention in the new drug development process. The present study aimed to identify potential marine-derived inhibitors against the target proteins of COVID-19 using a computational approach. Currently, 16 marine clinical-level compounds were selected for computational screening against the 4 SARS-CoV-2 main proteases. Computational screening resulted from the best drug candidates for each target based on the binding affinity scores and amino acid interactions. Among these, five marine-derived compounds, namely, chrysophaentin A (-6.6 kcal/mol), geodisterol sulfates (-6.6 kcal/mol), hymenidin (-6.4 kcal/mol), plinabulin (-6.4 kcal/mol), and tetrodotoxin (-6.3 kcal/mol) expressed minimized binding energy and molecular interactions, such as covalent and hydrophobic interactions, with the SARS CoV-2 main protease. Using molecular dynamic studies, the root-mean-square deviation (RMSD), root-mean-square fluctuation (RMSF), radius of gyration (ROG), and hydrogen bond (H-Bond) values were calculated for the SARS-CoV-2 main protease with a hymenidin docked complex. Additionally, in silico drug-likeness and pharmacokinetic property assessments of the compounds demonstrated favorable druggability. These results suggest that marine natural compounds are capable of fighting SARS-CoV-2. Further in vitro and in vivo studies need to be carried out to confirm their inhibitory potential.
ABSTRACT
Coronavirus Disease-2019 (COVID-19), a viral disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) was declared a global pandemic by WHO in 2020. In this scenario, SARS-CoV-2 main protease (COVID-19 Mpro), an enzyme mainly involved in viral replication and transcription is identified as a crucial target for drug discovery. Traditionally used medicinal plants contain a large amount of bioactives and pave a new path to develop drugs and medications for COVID-19. The present study was aimed to examine the potential of Emblica officinalis (amla), Phyllanthus niruri Linn. (bhumi amla) and Tinospora cordifolia (giloy) bioactive compounds to inhibit the enzymatic activity of COVID-19 Mpro. In total, 96 bioactive compounds were selected and docked with COVID-19 Mpro and further validated by molecular dynamics study. From the docking and molecular dynamics study, it was revealed that the bioactives namely amritoside, apigenin-6-C-glucosyl7-O-glucoside, pectolinarin and astragalin showed better binding affinities with COVID-19 Mpro. Drug-likeness, ADEMT and bioactivity score prediction of best drug candidates were evaluated by DruLiTo, pkCSM and Molinspiration servers, respectively. Overall, the in silico results confirmed that the validated bioactives could be exploited as promising COVID-19 Mpro inhibitors.