Natural flavonoid pectolinarin computationally targeted as a promising drug candidate against SARS-CoV-2

Abstract

Coronavirus disease-2019 (COVID-19) has become a global pandemic, necessitating the development of new medicines. In this investigation, we identified potential natural flavonoids and compared their inhibitory activity against spike glycoprotein, which is a target of SARS-CoV-2 and SARS-CoV. The target site for the interaction of new inhibitors for the treatment of SARS-CoV-2 has 82% sequence identity and the remaining 18% dissimilarities in RBD S1-subunit, S2-subunit, and 2.5% others. Molecular docking was employed to analyse the various binding processes used by each ligand in a library of 85 natural flavonoids that act as anti-viral medications and FDA authorised treatments for COVID-19. In the binding pocket of the target active site, remdesivir has less binding interaction than pectolinarin, according to the docking analysis. Pectolinarin is a natural flavonoid isolated from Cirsiumsetidensas that has anti-cancer, vasorelaxant, anti-inflammatory, hepatoprotective, anti-diabetic, anti-microbial, and anti-oxidant properties. The S-glycoprotein RBD region (330-583) is inhibited by kaempferol, rhoifolin, and herbacetin, but the S2 subunit (686-1270) is inhibited by pectolinarin, morin, and remdesivir. MD simulation analysis of S-glycoprotein of SARS-CoV-2 with pectolinarin complex at 100ns based on high dock-score. Finally, ADMET analysis was used to validate the proposed compounds with the highest binding energy.

Keywords: Computational analysis; Coronaviruses; Motif; S-glycoproteins; SARS-CoV2.

Graphical abstract

Fig. 1

3D model structure of SARS-CoV2 and their different domains: It is the schematic representation of S glycoprotein of SARS-CoV2 3D model structure and their different domains. Domains are arranged from N-terminal to C-terminal were colored coded in line representation is same in 3D model structure. This picture was generated by the PyMOL.

Fig. 2

Docking analysis of SARS-CoV-2 with pectolinarin It shows the detailed view of docking analysis of S glycoprotein of SARS-CoV-2 with flavonoid pectolinarin shows the highest dock score is −51.91 and also highest number of H-bond is 6, protein shown in red color surface view. In box is the detailed view of protein represented in multicolour cartoon form and pectolinarin is represented in green and red color stick form is carbon and oxygen respectively. The S2 subunit of SARS-CoV2-SP (red stick) which involved in formation of 6 H-bonding with pectolinarin and blue stick is involved in formation of 2 salt bridges formation residues are R1107 and K1211. Picture is generated from PyMOL visualization tool. (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)

Fig. 3

Docking analysis of SARS-CoV-2 with remdesivir It shows the full view of docking analysis of S glycoprotein of SARS-CoV-2 shown in cyan color (surface view) with FDA approved drug in COVID-19 patients as a treatment i.e. remdesivir shows the highest dock score is −46.03 in all FDA approved drug shown in blue color. In box is the detailed view of protein represented in cyan color cartoon form and remdesivir is represented in blue stick form respectively. The S2 subunit of SP-SARS-CoV2 is involved in formation of 3 H-bond with involved residues are N907, T912 and Q1113. Picture is generated from PyMOL visualization tool. (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)

Fig. 4

Molecular dynamics simulation: Backbone RMSD of SARS-CoV-2. The yellow curve represents the backbone RMSDs for 100 ns simulations. The red curve represents the RMSF for the 100 ns MD simulation. (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)

Fig. 5

Radius of gyration: The radius of gyration of the SARS-CoV-2-model backbone.

Fig. 6

Molecular dynamics simulation of S glycoprotein of SARS-CoV-2 with pectolinarin complex: It shows the time average structure of S glycoprotein of SARS-CoV-2 with pectolinarin complex.