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

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-3ß-ol, 3ß, 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.

Computational and Biological Investigations on Abl1 Tyrosine Kinase: A Review.

Abl1 tyrosine kinase is a validated target for the treatment of chronic myeloid leukemia. It is a form of cancer that is difficult to treat and much research is being done to identify new molecular entities and to tackle drug resistance issues. In recent years, drug resistance of Abl1 tyrosine kinase has become a major healthcare concern. Second and third-generation TKI reported better responses against the resistant forms; still they had no impact on long-term survival prolongation. New compounds derived from natural products and organic small molecule inhibitors can lay the foundation for better clinical therapies in the future. Computational methods, experimental and biological studies can help us understand the mechanism of drug resistance and identify novel molecule inhibitors. ADMET parameters analysis of reported drugs and novel small molecule inhibitors can also provide valuable insights. In this review, available therapies, point mutations, structure-activity relationship and ADMET parameters of reported series of Abl1 tyrosine kinase inhibitors and drugs are summarised. We summarise in detail recent computational and molecular biology studies that focus on designing drug molecules, investigation of natural product compounds and organic new chemical entities. Current ongoing research suggests that selective targeting of Abl1 tyrosine kinase at the molecular level to combat drug resistance in chronic myeloid leukemia is promising.