Evaluation of Cordyceps militaris steroids as anti-inflammatory agents to combat the Covid-19 cytokine storm: a bioinformatics and structure-based drug designing approach

Abstract

Since the SARS-CoV-2 epidemic, researchers have been working on figuring out ways to tackle multi-organ failure and hyperinflation, which are brought on by a cytokine storm. Angiotensin-converting enzyme 2 (ACE2), a SARS-CoV-2 spike glycoprotein’s cellular receptor, is involved in complicated molecular processes that result in hyperinflammation. Cordyceps militaris is one of the traditional Chinese medicines that is used as an immune booster, and it has exhibited efficacy in lowering blood glucose levels, seminal emissions, and infertility. In the current study, we explored the potential of Cordyceps militaris steroids as key agents in managing the anger of cytokine storm in Covid-19 using network ethnopharmacological techniques and structure-based drug designing approaches. The steroids present in Cordyceps militaris were initially screened against the targets involved in inflammatory pathways. The results revealed that out of 16 steroids, 5 may be effective against 17 inflammatory pathways by targeting 11 pathological proteins. Among the five steroids, beta-sitosterol, Cholest-5-en-3β-ol, 3β, and 7α-Dihydroxycholest-5-ene were found to interact with thrombin (F2), an important protein reported to reduce the severity of inflammatory mediators and Cholest-4-en-3-one was found to target Glucocorticoid receptor (NR3C1). The top docked steroid displayed key interactions with both targets, which retained key interactions throughout the 100 ns simulation period. These compounds were also shown high binding free energy scores in water swap studies. Based on obtained results the current study suggests the use of Cordyceps militaris as an add-on therapy that may reduce the progression of inflammatory co-morbidities among patients infected with SARS-CoV-2.

Communicated by Ramaswamy H. Sarma

Keywords:

• Network ethnopharmacology
• Cordyceps militaris
• anti-inflammatory
• SARS CoV-2
• binding DB

Acknowledgment

The authors would like to acknowledge the Ambrosia Food Farm Co, Bhowali - Bhimtal Rd, Bhowali, Sukha, Uttarakhand 263132 for providing consultancy project to Prof. Om Silakari. Authors also thanks Department of Biotechnology, New Delhi for providing a Bioinformatics centre facility in terms of Hardware and Software.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was financially supported by the Ambrosia Food Farm Co, Bhowali - Bhimtal Rd, Bhowali, Sukha, Uttarakhand 263132 and Department of Biotechnology (DBT), New Delhi [BT/PR39876/BTIS/137/7/2021].