Targeting COVID-19 (SARS-CoV-2) main protease through active phytocompounds of ayurvedic medicinal plants - Emblica officinalis (Amla), Phyllanthus niruri Linn. (Bhumi Amla) and Tinospora cordifolia (Giloy) - A molecular docking and simulation study

Selvakumar Murugesan; Sanjay Kottekad; Inchara Crasta; Sivakumar Sreevathsan; Dandamudi Usharani; Madan Kumar Perumal; Sandeep Narayan Mudliar

doi:10.1016/j.compbiomed.2021.104683

Targeting COVID-19 (SARS-CoV-2) main protease through active phytocompounds of ayurvedic medicinal plants - Emblica officinalis (Amla), Phyllanthus niruri Linn. (Bhumi Amla) and Tinospora cordifolia (Giloy) - A molecular docking and simulation study

Comput Biol Med. 2021 Sep:136:104683. doi: 10.1016/j.compbiomed.2021.104683. Epub 2021 Jul 24.

Authors

Selvakumar Murugesan¹, Sanjay Kottekad², Inchara Crasta¹, Sivakumar Sreevathsan³, Dandamudi Usharani², Madan Kumar Perumal⁴, Sandeep Narayan Mudliar⁵

Affiliations

¹ Plant Cell Biotechnology Department, CSIR-Central Food Technological Research Institute, Mysuru, 570 020, Karnataka, India.
² Department of Food Safety and Analytical Quality Control Laboratory, CSIR-Central Food Technological Research Institute, Mysuru, 570 020, Karnataka, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201 002, Uttar Pradesh, India.
³ Plant Cell Biotechnology Department, CSIR-Central Food Technological Research Institute, Mysuru, 570 020, Karnataka, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201 002, Uttar Pradesh, India.
⁴ Department of Biochemistry, CSIR-Central Food Technological Research Institute, Mysuru, 570 020, Karnataka, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201 002, Uttar Pradesh, India.
⁵ Plant Cell Biotechnology Department, CSIR-Central Food Technological Research Institute, Mysuru, 570 020, Karnataka, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201 002, Uttar Pradesh, India. Electronic address: sandeepm@cftri.res.in.

Abstract

Coronavirus Disease-2019 (COVID-19), a viral disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) was declared a global pandemic by WHO in 2020. In this scenario, SARS-CoV-2 main protease (COVID-19 M^pro), an enzyme mainly involved in viral replication and transcription is identified as a crucial target for drug discovery. Traditionally used medicinal plants contain a large amount of bioactives and pave a new path to develop drugs and medications for COVID-19. The present study was aimed to examine the potential of Emblica officinalis (amla), Phyllanthus niruri Linn. (bhumi amla) and Tinospora cordifolia (giloy) bioactive compounds to inhibit the enzymatic activity of COVID-19 M^pro. In total, 96 bioactive compounds were selected and docked with COVID-19 M^pro and further validated by molecular dynamics study. From the docking and molecular dynamics study, it was revealed that the bioactives namely amritoside, apigenin-6-C-glucosyl7-O-glucoside, pectolinarin and astragalin showed better binding affinities with COVID-19 M^pro. Drug-likeness, ADEMT and bioactivity score prediction of best drug candidates were evaluated by DruLiTo, pkCSM and Molinspiration servers, respectively. Overall, the in silico results confirmed that the validated bioactives could be exploited as promising COVID-19 M^pro inhibitors.

Keywords: COVID-19; Main protease; Medicinal plants; Molecular docking; Molecular dynamics; SARS-CoV-2.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

COVID-19
Coronavirus 3C Proteases / antagonists & inhibitors
Humans
Medicine, Ayurvedic
Molecular Docking Simulation
Molecular Dynamics Simulation
Peptide Hydrolases
Phyllanthus emblica* / chemistry
Phyllanthus* / chemistry
Phytochemicals / pharmacology
Plants, Medicinal / chemistry
Protease Inhibitors / pharmacology*
SARS-CoV-2 / drug effects*
Tinospora* / chemistry

Substances

Phytochemicals
Protease Inhibitors
Peptide Hydrolases
3C-like proteinase, SARS-CoV-2
Coronavirus 3C Proteases