In-silico studies on wild orange (Citrus macroptera Mont.) compounds against COVID-19 pro-inflammation targets

Abstract

One-fifth of COVID-19 patients suffer a severe course of COVID-19 (SARS-CoV-2) infection; however, the specific causes remain unclear. Despite numerous papers that have been flooded in different scientific journals clear clinical picture of COVID-19 aftermath persists to remain fuzzy. The survivors of severe COVID-19infection having defeated the virus are just the starting of an uncharted recovery path. Currently, there is no drug available that is safe to consume to combat this pandemic. However, researchers still struggling to find specific therapeutic solutions. The present study employed an in silico approach to assessing the inhibitory potential of the phytochemicals obtained from GC-MS analysis of Citrus macroptera against inflammatory proteins like COX-2, NMDAR and VCAM-1 which remains in a hyperactive state even after a patient is fully cured of this deadly mRNA virus. An extensive molecular docking investigation of the phyto-compounds at the active binding pockets of the inflammatory proteins revealed the promising inhibitory potential of the phytochemicals. Reasonable physicochemical attributes of the compounds following Lipinski’s rule of five, VEBER and PAINS analysis further established them as potential therapeutic candidates against aforesaid inflammatory proteins. MM-GBSA binding free energy estimation revealed that Limonene was the most promising candidate displaying the highest binding efficacy with the concerned VCAM-1 protein included in the present analysis. An interesting finding is the phytochemicals exhibited better binding energy scores with the concerned COX-2, VCAM-1 and NMDA receptor proteins than the conventional drugs that are specifically targeted against them. Our in silico results suggest that all the natural phyto-compounds derived from C. macroptera could be employed in Post covid inflammation complexities after appropriate pre-clinical and clinical trials for further scientific validation.

Communicated by Ramaswamy H. Sarma

Keywords:

• Post SARS-CoV-2
• C. macroptera
• molecular docking
• Limonene
• drug-likeness
• MM-GBSA
• molecular dynamics simulations

Acknowledgment

ML acknowledges CSIR for providing fellowship to execute this work. AS, CG, IS and SB acknowledges the University of North Bengal, West Bengal, India for the infrastructure support to the work.

Disclosure statement

The authors have declared there is no conflict of interest.

Funding

The author(s) reported there is no funding associated with the work featured in this article.

Authors’ contribution

IS and AS conceived the idea. ML, SB designed the experiments and performed the tests and did all the docking processes. IS performed the molecular simulation study. ML, SB, IS, CG prepared the manuscript. All authors agreed with the final version of the manuscript.