Structure-based screening of novel lichen compounds against SARS Coronavirus main protease (Mpro) as potentials inhibitors of COVID-19

Abstract

The outbreak of SARS-CoV-2 and deaths caused by it all over the world have imposed great concern on the scientific community to develop potential drugs to combat Coronavirus disease-19 (COVID-19). In this regard, lichen metabolites may offer a vast reservoir for the discovery of antiviral drug candidates. Therefore, to find novel compounds against COVID-19, we created a library of 412 lichen compounds and subjected to virtual screening against the SARS-CoV-2 Main protease (Mpro). All the ligands were virtually screened, and 27 compounds were found to have high affinity with Mpro. These compounds were assessed for drug-likeness analysis where two compounds were found to fit well for redocking studies. Molecular docking, drug-likeness, X-Score, and toxicity analysis resulting in two lichen compounds, Calycin and Rhizocarpic acid with Mpro-inhibiting activity. These compounds were finally subjected to molecular dynamics simulation to compare the dynamics behavior and stability of the Mpro after ligand binding. The binding energy was calculated by MM-PBSA method to determine the intermolecular protein-ligand interactions. Our results showed that two compounds; Calycin and Rhizocarpic acid had the binding free energy of − 42.42 kJ mol/1 and − 57.85 kJ mol/1 respectively as compared to reference X77 (− 91.78 kJ mol/1). We concluded that Calycin and Rhizocarpic acid show considerable structural and pharmacological properties and they can be used as hit compounds to develop potential antiviral agents against SARS-CoV-2. These lichen compounds may be a suitable candidate for further experimental analysis.

Predictive modeling by deep learning, virtual screening and molecular dynamics study of natural compounds against SARS-CoV-2 main protease

“…Met49, Cys145, and Met165 showed higher binding affinity as compared to other residues. The results revealed that Met49, Cys145, and Met165 play an important role in Mpro-ligand stabilization which is in agreement in a previous study (Joshi, Sharma, et al., 2020 ).…”

“…Many studies have proven that natural compounds are very effective to find potential drug candidates against different viral diseases. A recent study suggests that some natural compounds may be helpful for the treatment of COVID-19 infection (Joshi, Sharma, et al., 2020 ; Kumar et al., 2020 ). In vitro tests have reported that natural compound lycorine isolated from Lycoris radiata extract is candidates for the development of new anti-SARS-CoV drugs in the treatment of SARS (Li et al., 2005 ).…”

“…The MD Simulation study of Mpro and screened ligand-protein complexes was performed using GROMACS 5.0 (Pronk et al., 2013 ) package of Molecular Dynamics as described in a publication (Joshi, Sharma, et al., 2020 ). MD Simulation was performed on a work station with configuration Ubuntu 16.04 LTS 64-bit, 8GB RAM, Intel®CoreTM i7-9900K CPU, and 6 GB GPU.…”

Potential therapeutic use of corticosteroids as SARS CoV-2 main protease inhibitors: a computational study

“…These two crystal structures also laid the basis toward the structure-based drug design against Mpro. Many small molecules are being proposed as effective SARS CoV-2 Mpro inhibitor (Bhardwaj et al, 2020 ; Das et al, 2020 ; Ghosh et al, 2020a , 2020b ; Gorla et al, 2020 ; Gurung et al, 2020 ; Joshi et al, 2020 a, 2020 b; Mazzini et al, 2020 ). Several anti-HIV drugs (darunavir, lopinavir, atazanavir, etc.)…”

“…Thus, they have revealed, both the structures of substrate-binding site of Mpro as well as structure-based approach for designing potential drug molecules against COVID-19. Based on these, natural products and phytochemicals have been studied to find an effective inhibitor of Mpro (Bhardwaj et al, 2020 ; Das et al, 2020 ; Ghosh et al, 2020a , 2020b ; Gorla et al, 2020 ; Gurung et al, 2020 ; Joshi et al, 2020a , 2020b ; Mazzini et al, 2020 ).…”