Target prediction, computational identification, and network-based pharmacology of most potential phytoconstituent in medicinal leaves of Justicia adhatoda against SARS-CoV-2

Abstract

The current global epidemic of the novel coronavirus (SARS-CoV-2) has been labeled a global public health emergency since it is causing substantial morbidity and mortality on daily basis. We need to identify an effective medication against SARS-CoV-2 because of its fast dissemination and re-emergence. This research is being carried out as part of a larger strategy to identify the most promising therapeutic targets using protein-protein interactions analysis. Mpro has been identified as one of the most important therapeutic targets. In this study, we did in-silico investigations to identify the target and further molecular docking, ADME, and toxicity prediction were done to assess the potential phyto-active antiviral compounds from Justicia adhatoda as powerful inhibitors of the Mpro of SARS-COV-2. We also investigated the capacity of these molecules to create stable interactions with the Mpro using 100 ns molecular dynamics simulation. The highest scoring compounds (taraxerol, friedelanol, anisotine, and adhatodine) were also found to exhibit excellent solubility and pharmacodynamic characteristics. We employed MMPBSA simulations to assess the stability of docked molecules in the Mpro binding site, revealing that the above compounds form the most stable complex with the Mpro. Network-based Pharmacology suggested that the selected compounds have various modes of action against SARS-CoV-2 that include immunoreaction enrichment, inflammatory reaction suppression, and more. These findings point to a promising class of drugs that should be investigated further in biochemical and cell-based studies to see their effectiveness against nCOVID-19.

Communicated by Ramaswamy H. Sarma

Keywords:

• Computational identification
• molecular dynamics
• network-based pharmacology
• Justicia adhatoda
• nCOVID-19
• ADMET

Acknowledgments

This work was supported by our Department of Pharmaceutical Sciences & Technology, Birla Institute of Technology, Mesra, Ranchi, Jharkhand—835215 (India). We thank the Department of Chemistry, Birla Institute of Technology, Mesra, Ranchi, Jharkhand—835215 (India) for providing the necessary software to carry out the study. We also would like to thank the Department of Medical Laboratory Technology, Al-Nisour University College, Baghdad, Iraq for providing the necessary software to carry out the study.

Disclosure statement

The authors declare no conflict of interest.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Additional information

Notes on contributors

Pankaj Dagur

All authors contributed to the study conception, creation of theory and design. Khattab Al-Khafaji, Gourav Rakshit and Pankaj Dagur equally contributed, to the writing of the manuscript, preparation, data collection, software, molecular docking, molecular dynamics simulation studies, MMPBSA calculations, target prediction, network pharmacology, and reference collection. Sheikh Murtuja, Abanish Biswas and Parineeta Jha contributed to the writing of the manuscript, evaluating the results of the performed studies and reviewing the correctness of the manuscript. Manik Ghosh concieved, constantly monitored, supervised, reviewed and edited all the versions of the manuscript and supported this research work with all necessary guidance and permissions. The first draft of the manuscript was written by Gourav Rakshit, Pankaj Dagur and Khattab Al-Khafaji and all authors commented on previous versions of the manuscript. All the authors have read and further approved the final manuscript.

Murtuja Sheikh

All authors contributed to the study conception, creation of theory and design. Khattab Al-Khafaji, Gourav Rakshit and Pankaj Dagur equally contributed, to the writing of the manuscript, preparation, data collection, software, molecular docking, molecular dynamics simulation studies, MMPBSA calculations, target prediction, network pharmacology, and reference collection. Sheikh Murtuja, Abanish Biswas and Parineeta Jha contributed to the writing of the manuscript, evaluating the results of the performed studies and reviewing the correctness of the manuscript. Manik Ghosh concieved, constantly monitored, supervised, reviewed and edited all the versions of the manuscript and supported this research work with all necessary guidance and permissions. The first draft of the manuscript was written by Gourav Rakshit, Pankaj Dagur and Khattab Al-Khafaji and all authors commented on previous versions of the manuscript. All the authors have read and further approved the final manuscript.

Khattab Al-Khafaji

All authors contributed to the study conception, creation of theory and design. Khattab Al-Khafaji, Gourav Rakshit and Pankaj Dagur equally contributed, to the writing of the manuscript, preparation, data collection, software, molecular docking, molecular dynamics simulation studies, MMPBSA calculations, target prediction, network pharmacology, and reference collection. Sheikh Murtuja, Abanish Biswas and Parineeta Jha contributed to the writing of the manuscript, evaluating the results of the performed studies and reviewing the correctness of the manuscript. Manik Ghosh concieved, constantly monitored, supervised, reviewed and edited all the versions of the manuscript and supported this research work with all necessary guidance and permissions. The first draft of the manuscript was written by Gourav Rakshit, Pankaj Dagur and Khattab Al-Khafaji and all authors commented on previous versions of the manuscript. All the authors have read and further approved the final manuscript.

Manik Ghosh

All authors contributed to the study conception, creation of theory and design. Khattab Al-Khafaji, Gourav Rakshit and Pankaj Dagur equally contributed, to the writing of the manuscript, preparation, data collection, software, molecular docking, molecular dynamics simulation studies, MMPBSA calculations, target prediction, network pharmacology, and reference collection. Sheikh Murtuja, Abanish Biswas and Parineeta Jha contributed to the writing of the manuscript, evaluating the results of the performed studies and reviewing the correctness of the manuscript. Manik Ghosh concieved, constantly monitored, supervised, reviewed and edited all the versions of the manuscript and supported this research work with all necessary guidance and permissions. The first draft of the manuscript was written by Gourav Rakshit, Pankaj Dagur and Khattab Al-Khafaji and all authors commented on previous versions of the manuscript. All the authors have read and further approved the final manuscript.