Leucoefdin a potential inhibitor against SARS CoV-2 Mpro

Abstract

Leucoefdin an important constituent of various fruits such as banana, raspberry, etc. was explored to target M^Pro protease of SARS Co-V 2. Ligand was found to bind at active site of M^Pro with large negative binding energies in molecular docking and simulation study. The docking results showed that Leucoefdin interacted with the M^Pro by forming hydrogen bonds, at Leu 141, His163, His 164, and Glu 166. Other non-bonded interactions were seen at Met49, Pro52, Tyr54, Phe140, Leu141, Cys145 and Met165. Results of Leucoefdin was in coherence with the recently reported M^Pro protease-inhibitor complex. It even displayed better binding energies (kcal/mol) in HTVS (-6.28), SP (-7.28), XP (-9.29) and MMGBSA (-44.71) as compared to the reference ligand [HTVS (-4.87), SP (-6.79), XP (-5.75) and MMGBSA (-47.76)]. Leucoefdin-M^Pro complex on molecular dynamic simulation showed initial fluctuations in RMSD plot for a certain period and attained equilibrium which remained stable during entire simulation for 150 ns. RMSF of protein showed less secondary structure fluctuations and a greater number of H-bond formation with Leucoefdin during 150 ns simulation. Post simulation MMGBSA analysis showed binding energy of -45.98 Kcal/mol. These findings indicated the potential of Leucoefdin as lead compound in R&D for drug discovery and development against SARS CoV-2.Communicated by Ramaswamy H. Sarma.

Keywords: Leucoefdin; MPro; SARS CoV-2; docking; simulation.

Figure 1.

Protein ligand interaction study using Glide for (a) Reference (Z31792168) Ligand M^Pro complex; (b) M^Pro with Leucoefdin.

Figure 2.

RMSD profile of M Pro and Leucoefdin during 150 ns MD simulation.

Figure 3.

RMSF study to show local changes around protein chain in 150 ns simulation (green bar shows ligand contact sites).

Figure 4.

Secondary structure composition during entire 150 ns simulation (red-ɑ helices, blue-βstrands, white-loop).

Figure 5.

Timeline representation of the interaction and contacts, top panel show specific contact of ligand and protein during 150 ns simulation.

Figure 6.

(a) Protein ligand interaction study during 150 ns simulation(green-Hbond; pink-ionic; blue-water bridges; violet-Hydrophobic); (b) Schematic ligand interaction with protein red charged, green hydrophobic, blue polar,·−· salt bridge during simulation.