Targeting β-glucan synthase for Mucormycosis “The 'black fungus” maiming Covid patients in India: computational insights
Black fungus also known as Mucormycosis, has recently devastated some states of India. It has been declared pandemic now. Inhibitors of glucon synthesis pathways have been evaluated to curtail the Mucormycosis but still at infancy stage. Due to key role in glucon synthesis, in the present study β -glucan synthase has been regarded as a suitable target for drug design. In-silico docking and pharmacological study was designed to evaluate the effect of potent bioactive molecule 1-8 cineole present in essential oils of eucalyptus plant leaves against β -glucan synthase enzyme. Till date there is no work is undertaken on in-silico analysis of this compound against β -glucan synthase. Patch-dock analysis was used for docking. Ligand Protein 2D and 3D Interactions were also studied. Drug likes and toxicity profile was also evaluated. Cancer cell line toxicity profile was also studied. The calculated parameters such as docking score indicated effective binding of 1-8 cineole to β -glucan synthase -protein. Interactions results indicated that, β -glucan synthase enzyme and 1-8 cineole complexes forms hydrogen and hydrophobic interactions. 1-8 cineole also depicted sufficient level of cancer cell line toxicity. Drug likeliness profiles by assaying absorption, distribution, metabolism, excretion and toxicity (ADMET) studies provided guidelines and mechanistic scope for identification of 1-8 cineole as potent anti-fungal drug. Therefore, essential oil from eucalyptus may represent potential herbal treatment to act as anti-fungal drug.
Keywords: COVID-19, black fungus, Eucalyptus oil, Herbal Drug
2. Zavrel M, White T C, "Medically important fungi respond to azole drugs: an update" Future Microbiol., 2015; 10:1355-1373. https://doi.org/10.2217/FMB.15.47
3. Cuenca-Estrella M, "Antifungal drug resistance mechanisms in pathogenic fungi: from bench to bedside" Clin. Microbiol. Infect, 2014; 20:54-59. https://doi.org/10.1111/1469-0691.12495
4. Chen Xueqi, Zewen Zhang, Zuozhong Chen, Yiman Li, Shan Su, Shujuan Sun," Potential Antifungal Targets Based on Glucose Metabolism Pathways of Candida albicans" Front Microbio, 2020, article 296. https://doi.org/10.3389/fmicb.2020.00296
5. Han X, Zhu X, Hong Z, Wei L, Ren Y, Wan F, et al., " Structure-based rational design of novel inhibitors against fructose-1,6-bisphosphate aldolase from Candida albicans". J. Chem. Inf. ModelI, 2017; 57:1426-1438 https://doi.org/10.1021/acs.jcim.6b00763
6. Gong Y, Li T, Yu C, Sun S, " Candida albicans heat shock proteins and Hsps-associated signaling pathways as potential antifungal targets" Front. Cell. Infect. Microbiol, 2017; 7:520 https://doi.org/10.3389/fcimb.2017.00520
7. Sebei et al. "Chemical composition and antibacterial activities of seven Eucalyptus species essential oils leaves" Biological Research, 2015; 48:7. https://doi.org/10.1186/0717-6287-48-7
8. Elaissi A, Bel Haj Salah K, Mabrouk S, Chemli R, Harzallah-Skhiri F "Antibacterial activity and chemical composition of 20 Eucalyptus species essential oils". Food Chem 2011; 129:1427-1434 https://doi.org/10.1016/j.foodchem.2011.05.100
9. Ramezani H, Singh HP, Batish DR, Kohli RK "Antifungal activity of the volatile oil of Eucalyptus citriodora" Fitoterapia, 2002; 73:261-262 https://doi.org/10.1016/S0367-326X(02)00065-5
10. Sartorelli P, Marquioreto AD, Amaral-Baroli A, Lima ME, Moreno PR "Chemical composition and antimicrobial activity of the essential oils from two species of Eucalyptus" Phytother Res 2007; 21:231-233. https://doi.org/10.1002/ptr.2051
11. Tyagi AK, Malik A "Antimicrobial potential and chemical composition of Eucalyptus globulus oil in liquid and vapour phase against food spoilage microorganisms" Food Chem, 2011; 126:228-235. https://doi.org/10.1016/j.foodchem.2010.11.002
12. Liu J, Balasubramanian MK "1,3-beta-Glucan synthase: a useful target for antifungal drugs" Curr Drug Targets Infect Disord, 2001; 1:159-69. https://doi.org/10.2174/1568005014606107
13. Yun Hui Yang, Hyeon-Woo Kang, Hyeon-Su Ro, Cloning and Molecular Characterization of β-1,3-Glucan Synthase from Sparassis crispa, Mycobiology, 2014; 42:167-173 https://doi.org/10.5941/MYCO.2014.42.2.167
14. Wu C, Liu Y, Yang Y, Zhang P, Zhong W, Wang Y, Wang Q, et al., Analysis of therapeutic targets for SARS-CoV-2 and discovery of potential drugs by computational methods" Acta Pharmaceutica Sinica B, 2020; 10:766-788. https://doi.org/10.1016/j.apsb.2020.02.008
15. Web resources: https://bit.ly/3hFLgWs, https://bbc.in/3f0ijmv, https://bit.ly/2RrcFRw, https://bit.ly/3ypZpgx
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0). that allows others to share the work with an acknowledgment of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgment of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).