In-silico Identification of citrus phytochemicals for chemical interaction of CotH of Mucor and human GRP78 receptor and its experimental verification through FTIR spectroscopy

Abstract

After suffering from serious critical disease such as recent COVID-19 pandemic, secondary fungal infection (Specially Mucormycosis) has become a serious concern throughout the world. Glucose regulated protein 78 (GRP78) is a multifunctional protein which acts as a receptor in human body for spore Coat homolog (CotH) cell surface protein of Mucorales. The development of immunity with easily available plant products is vital and essential due to having less effect on other biological activities. Here, In-silico method has been employed to screen antifungal citrus phyto-chemicals through molecular docking with CotH and its ADMET study due its rapid and cost effective quality compared to the trial and error methods using experimental studies. Limonin and naringin have been selected as potential ligands due to having its low binding affinity and no risk factor as per Lipinski's rule of five and medicinal chemistry. Molecular interaction of naringin and limonin with CotH obtained by molecular docking shows better binding affinity of -8.7 and – 8.9 kcal/mol respectively. The binding of CotH-GRP78 complex (developed through protein-protein molecular docking) with limonin resists more in the spreading of Mucormycosis in comparison to naringin. The FTIR spectra of limonin-CotH and Naringin-CotH sample exhibits the evidences of hydrogen bond for the formation of both strong limonin-CotH and naringin-CotH complex assuring the development of immunity with citrus fruit containing limonin and naringin.