Biflavonoids from <i>Rhus succedanea</i> as probable natural inhibitors against SARS-CoV-2: a molecular docking and molecular dynamics approach
Creators: name: Lokhande, Kiran
name: Nawani, Neelu
name: Venkateswara, Swamy K.
name: Pawar, Sarika
Publisher: name: Taylor & Francis
Year: 2020
Subjects: subject: Biophysics
subject: Biochemistry
subject: Medicine
subject: Molecular Biology
subject: Pharmacology
subject: Biotechnology
subject: 39999 Chemical Sciences not elsewhere classified
subject: FOS: Chemical sciences
subject: 69999 Biological Sciences not elsewhere classified
subject: FOS: Biological sciences
subject: Cancer
subject: 110309 Infectious Diseases
subject: FOS: Health sciences
subject: 60506 Virology
subject: Computational Biology

description: 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 <i>Rhus succedanea</i> 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 <i>Rhus succedanea</i> 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 <i>in vitro</i> and <i>in vivo</i>, which is necessary for the therapeutic development of novel and safe drugs to control SARS-CoV-2. Communicated by Ramaswamy H. Sarma Research highlights<i>Rhus succedanea</i> 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. <i>Rhus succedanea</i> 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.