Biflavonoids from Rhus succedanea as probable natural inhibitors against SARS-CoV-2: a molecular docking and molecular dynamics approach

Abstract

The recent outbreak of SARS-CoV-2 has quickly become a worldwide pandemic and generated panic threats for both the human population and the global economy. The unavailability of effective vaccines or drugs has enforced researchers to hunt for a potential drug to combat this virus. Plant-derived phytocompounds are of applicable interest in the search for novel drugs. Bioflavonoids from Rhus succedanea are already reported to exert antiviral activity against RNA viruses. SARS-CoV-2 Mpro protease plays a vital role in viral replication and therefore can be considered as a promising target for drug development. A computational approach has been employed to search for promising potent bioflavonoids from Rhus succedanea against SARS-CoV-2 Mpro protease. Binding affinities and binding modes between the biflavonoids and Mpro enzyme suggest that all six biflavonoids exhibit possible interaction with the Mpro catalytic site (−19.47 to −27.04 kcal/mol). However, Amentoflavone (−27.04 kcal/mol) and Agathisflavone (−25.87 kcal/mol) interact strongly with the catalytic residues. Molecular dynamic simulations (100 ns) further revealed that these two biflavonoids complexes with the Mpro enzyme are highly stable and are of less conformational fluctuations. Also, the hydrophobic and hydrophilic surface mapping on the Mpro structure as well as biflavonoids were utilized for the further lead optimization process. Altogether, our findings showed that these natural biflavonoids can be utilized as promising SARS-CoV-2 Mpro inhibitors and thus, the computational approach provides an initial footstep towards experimental studies in in vitro and in vivo , which is necessary for the therapeutic development of novel and safe drugs to control SARS-CoV-2. Communicated by Ramaswamy H. Sarma Research highlights Rhus succedanea biflavonoids have antiviral activity. The molecular interactions and molecular dynamics displayed that all six biflavonoids bound with a good affinity to the same catalytic site of Mpro. The compound Amentoflavone has a strong binding affinity (−27.0441 kcal/mol) towards Mpro. The binding site properties of SARS-CoV-2-Mpro can be utilized in a novel discovery and lead optimization of the SARS-CoV-2-Mpro inhibitor.

Comparative study of the interaction of ivermectin with proteins of interest associated with SARS-CoV-2: A computational and biophysical approach

“…4 D). There are few reports of DM of ivermectin versus Mpro, however, the results obtained in terms of RMSD of the Cα atoms of M pro in SARS-CoV-2 are related to those reported during the simulation period of 100 ns versus other compounds that also remained in the steady state at ≈ 3 Å RMSD [ 16 , 96 , 97 ].…”

De novo design and bioactivity prediction of SARS-CoV-2 main protease inhibitors using recurrent neural network-based transfer learning

“…In addition, an X-ray crystal structure of boceprevir complexed with M pro is available on PDB (PDB: 6WNP). Some of the top 10 molecules on Additional file 1 : Table S2 have been described in different in silico analysis showing their potential to bind to M pro , such as Novobiocin [ 61 ], Saquinavir [ 62 , 63 ], Aprepitant [ 64 ] and Leucovorin [ 65 ]. Nevertheless, confirmatory screens on these predicted hits are still lacking.…”

Interaction study of monoisoamyl dimercaptosuccinic acid with bovine serum albumin using biophysical and molecular docking approaches

“…All computational calculations were performed in the Schrodinger suite 2018-4. The crystal structure of BSA and equine serum albumin (ESA) was retrieved from the RCSB database https://academic.oup.com/nar/article/28/1/235/2384399 24 – 26 . ESA (PDB ID: 6U4X) 26 and BSA (PDB ID: 4F5S) 27 , 28 were prepared using Schrodinger protein preparation wizard and all ionizable residues were set to their probable protonation state at pH 7.4 using ProPka 29 .…”