Identification of phytocompounds from Houttuynia cordata Thunb. as potential inhibitors for SARS-CoV-2 replication proteins through GC–MS/LC–MS characterization, molecular docking and molecular dynamics simulation

Autor: Sanjib Kumar Das, Saurov Mahanta, Bhaben Tanti, Hui Tag, Pallabi Kalita Hui
Rok vydání: 2021
Předmět:
medicine.medical_treatment
Protein Data Bank (RCSB PDB)
Molecular dynamics
Molecular Dynamics Simulation
010402 general chemistry
01 natural sciences
Gas Chromatography-Mass Spectrometry
Catalysis
Inorganic Chemistry
chemistry.chemical_compound
Tandem Mass Spectrometry
Drug Discovery
medicine
Humans
Protease Inhibitors
Houttuynia
Physical and Theoretical Chemistry
Pandemics
Molecular Biology
SARS-CoV-2 proteins
Protease
biology
SARS-CoV-2
010405 organic chemistry
Drug discovery
Organic Chemistry
General Medicine
biology.organism_classification
Ligand (biochemistry)
GC–MS/LC–MS
Quercitrin
COVID-19 Drug Treatment
0104 chemical sciences
Houttuynia cordata
Molecular Docking Simulation
chemistry
Biochemistry
Docking (molecular)
Molecular docking
Original Article
Inhibitor phytocompounds
Chromatography
Liquid
Information Systems
Zdroj: Molecular Diversity
ISSN: 1573-501X
1381-1991
DOI: 10.1007/s11030-021-10226-2
Popis: Graphic abstract The COVID-19 pandemic caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a massive viral disease outbreak of international concerns. The present study is mainly intended to identify the bioactive phytocompounds from traditional antiviral herb Houttuynia cordata Thunb. as potential inhibitors for three main replication proteins of SARS-CoV-2, namely Main protease (Mpro), Papain-Like protease (PLpro) and ADP ribose phosphatase (ADRP) which control the replication process. A total of 177 phytocompounds were characterized from H. cordata using GC–MS/LC–MS and they were docked against three SARS-CoV-2 proteins (receptors), namely Mpro, PLpro and ADRP using Epic, LigPrep and Glide module of Schrödinger suite 2020-3. During docking studies, phytocompounds (ligand) 6-Hydroxyondansetron (A104) have demonstrated strong binding affinity toward receptors Mpro (PDB ID 6LU7) and PLpro (PDB ID 7JRN) with G-score of − 7.274 and − 5.672, respectively, while Quercitrin (A166) also showed strong binding affinity toward ADRP (PDB ID 6W02) with G-score -6.788. Molecular Dynamics Simulation (MDS) performed using Desmond module of Schrödinger suite 2020–3 has demonstrated better stability in the ligand–receptor complexes A104-6LU7 and A166-6W02 within 100 ns than the A104-7JRN complex. The ADME-Tox study performed using SwissADMEserver for pharmacokinetics of the selected phytocompounds 6-Hydroxyondansetron (A104) and Quercitrin (A166) demonstrated that 6-Hydroxyondansetron passes all the required drug discovery rules which can potentially inhibit Mpro and PLpro of SARS-CoV-2 without causing toxicity while Quercitrin demonstrated less drug-like properties but also demonstrated as potential inhibitor for ADRP. Present findings confer opportunities for 6-Hydroxyondansetron and Quercitrin to be developed as new therapeutic drug against COVID-19.
Databáze: OpenAIRE
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