Probing marine brown macroalgal phlorotannins as antiviral candidate against SARS-CoV-2: molecular docking and dynamics simulation approach

Abstract

Over the past year, owing to the emergent demand for the search for potential COVID-19 therapeutics, identifying alternative candidates from biological sources is one of the sustainable ways to reinforce the drug discovery process. Marine macroalgae have numerous advantages because of the richest availability of underexploited bioactive compounds. Polyphenolic compounds like phlorotannins obtained from brown macroalgae are reported as proven antiviral and immunostimulatory agents. Thus, the present study evaluated the possibility of phlorotannins as antagonists to the multiple target proteins essential for SARS-CoV-2 replication. Twenty different types of potent phlorotannins were targeted against druggable target proteins, viz., 3CLpro, RdRp, and Spro using AutoDock molecular docking, drug-likeness were assessed by ADMET profiling (Qik-Prop module). Further, validated with 200 ns molecular dynamics (MD) simulation (Desmond module) for the top-ranked phlorotannins based on docking binding affinities. Among the twenty phlorotannins studied, eckol hexacetate, phlorofucofuroeckol, fucofuroeckol, and bifuhalol-hexacetate showed significant binding affinities across the selected targets. Besides, MD simulations highlighted Glu166, Gln189, Cys145, and Thr190 tetrad as potential interaction sites to inhibit 3CLpro's activity. Moreover, phlorotannins were confirmed to be druglike, with no major deviation observed in ADMET-profiling. Hence, phlorotannins could be therapeutic candidates against SARS-CoV-2. However, further investigations are needed to prove its efficacy as an antiviral agent. Conclusively, this study may envisage that the novel finding could notably impact the advancement of antiviral interventions for COVID-19 in the near future.

Derivation, Functionalization of (S)-Goniothalamin from Goniothalamus wightii and Their Derivative Targets SARS-CoV-2 MPro, SPro, and RdRp: A Pharmacological Perspective

“…The docked ligand and protein interaction were examined using XP pose viewer to determine the optimistic pose, whereas the 2D-interaction diagram of a ligand–protein-complex molecule was obtained using the ligand-interaction module. Subsequently, the acquired XP pose was analyzed for the investigation of the binding interaction of ligand molecules upon the target protein [ 43 ]. From the 2 highest-ranked complex molecules, the MD simulation was performed using the Desmond module on the maestro platform of Schrodinger software.…”

Pentafuhalol-B, a Phlorotannin from Brown Algae, Strongly Inhibits the PLK-1 Overexpression in Cancer Cells as Revealed by Computational Analysis

“…The geometrical structures of phlorotannins (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15) and control drugs such as volasertib (16) were optimised by the B3LYP hybrid function with a 6-31 G basis set using the DFT method (Figure 1). DFT is the most commonly used computation based on quantum theory to optimise the electrical structures of isolated atoms or molecules.…”

“…These descriptors were comprised of ionisation energy (IE), electron affinity (EA), hardness (η), and softness (σ), which are involved in defining the chemical properties of a compound [22]. The calculated HOMO-LUMO gap, chemical descriptors, density of states (DOS), and molecular electrostatic map of all the selected phlorotannins and volasertib (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16) are displayed in Figures 2-4 as well as Table 1.…”

“…Phloroglucinol isolated from Himanthalia elongate demonstrated promising anti-microbial and antioxidant activities [8]. Some studies revealed that phlorotannins may act as antiviral agents by inhibiting human papillomavirus (HPV16PVs and HPV18PVs), influenza A like H1N1 and H9N2, human immunodeficiency virus type-1 (HIV-1), viral hemorrhagic septicemia virus (VHSV), murine norovirus (MNV), as well as coronaviruses [9]. An in vitro study showed that a phlorotannins-rich extract of brown seaweed, namely Saccharina japonica Aresch, inhibited the growth of human hepatocellular carcinoma cells (HepG2).…”

“…Gunaseelan et al identified many phlorotannins as alternative therapeutic agents against SARS-CoV-2 replicative proteins through molecular docking and MD simulation analysis using AutoDock Vina 1.5.6 version. They found that phlorotannins were involved in interacting with the Glu166, Gln189, Cys145, and Thr190 tetrad amino acid residues to inhibit 3CLpro activity [9]. Bakunina et al showed that phlorotannins, namely DP-15 oligophlorethol and heptaphlorethol obtained from brown algae Costaria costata, act as inhibitors through interactions with amino acid residues (Asp 156 and Asp 217) of human α-NaGalase in cancer cells [11].…”