Facing COVID-19 Via Anti-Inflammatory Mechanism of Action: Molecular Docking and Pharmacokinetic Studies of Six Anti-Inflammatory Compounds Derived from Passiflora edulis

Abstract

Aim: In the most severe case of the COVID-19, there is an excessive production of proinflammatory cytokines, being the main cause of mortality and morbidity. The present study aims at assessing the potential inhibitor effect of six phytochemicals with anti-inflammatory activity derived from Passiflora edulis, against the SARS-CoV-2 main protease.
 Materials and Methods: Virtual screening by molecular docking (Autodock tool) was used to obtain the binding energies of ligand-protein complexes formed between each of the six ligands and the SARS-CoV-2 main protease. The six ligands were then submitted to ADME (absorption, distribution, metabolism and excretion) and toxicity analyses to understand their pharmacokinetic behavior, using SwissADME, preADMET and pkCSM webservers.
 Results: Four high-docking score compounds were identified (both flavonoids) as hits, with the trend: ligand 4 (quercetin, -8.2 kcal/mol ) > ligand 1 (chrysin, -8.0 kcal/mol) > ligand 2 (kaempferol, -7.9 kcal/mol) > ligand 3 (luteolin, -7.7 kcal/mol)> ligand 5 (harmol, -6.7 kcal/mol) > ligand 6 (harmine, -6.4 kcal/mol). The pharmacokinetic behavior of the six ligands revealed that they can be easily absorbed and have good permeability and bioavailability. The toxicity predictions of the six compounds from P. edulis which is an editable fruit confirm that they are safe.
 Conclusion: Several approaches are currently being used to tackle the COVID-19. Given the cytokine storm in the most severe case of the COVID-19, we adopted the strategy of combatting the disease by compounds that exhibit anti-inflammatory activity. The assessment of the efficiency of six phytochemicals from P. edulis against the SARS-CoV-2 Mpro and their pharmacokinetic profile revealed their potential inhibitor effect against the COVID-19 protein.

SwissADME and pkCSM Webservers Predictors: an integrated Online Platform for Accurate and Comprehensive Predictions for In Silico ADME/T Properties of Artemisinin and its Derivatives

“…The goal of this study is to use SwissADME [10] and pkCSM [11] webservers to forecast the physicochemical qualities, drug-likeness properties, ADME (absorption, distribution, metabolism, and excretion), and toxicity of five artemisinin derivatives to understand their pharmacokinetic behaviour. In addition to being free, the webservers utilized in this work have undergone several comparison trials that show that SwissADME and pkCSM present as well as or improved than numerous other frequently used techniques [ [10], [11], [12], [13], [14], [15], [16]].…”

Antifungal plant flavonoids identified in silico with potential to control rice blast disease caused by Magnaporthe oryzae

“…The properties related to G-protein coupled receptors (GPCR), enzyme inhibitors (EI), kinase inhibitors (KI), nuclear receptor ligands (NRL), and ion channel modulators (ICM) were examined to determine the bioactivity scores [56,57]. Additionally, the SwissADME tool was employed to quickly establish the bioavailability of the ligands [58].…”

In silico drug repurposing of anticancer drug 5-FU and analogues against SARS-CoV-2 main protease: molecular docking, pharmacokinetics and chemical reactivity

“…Molecules or ligands bind to the active site of the target enzyme by forming interactions with the surface of the active site cavity, or better with some of the amino acid residues that form the active site cavity. In the particular case of the crystal structure of 3CLpro extracted from PDB, the binding cavity is defined by a series of important residues, namely THR24, THR25, PHE140, ASN142, GLY143, CYS145, HIS41, HIS163, HIS164, GLU166 and HIS172 [5,[39][40][41]. Ligands interacting with this protease as expected to develop a variety of interaction with some of these amino acids.…”