Title:An Insight into the Repurposing of Phytoconstituents obtained from
Delhi’s Aravalli Biodiversity Park as Antifungal Agents
Volume: 24
Issue: 7
Author(s): Amanpreet Kaur, Kalicharan Sharma, Neetika Sharma and Geeta Aggarwal*
Affiliation:
- Delhi Pharmaceutical Sciences and Research University, M.B. Road, Sector III, Pushp Vihar, New Delhi, 110017, India
Keywords:
Repurposing, antifungal, Sterol 14-α-demethylase, HSP-90, docking score, pre- and post-COVID.
Abstract: The global prevalence of fungal infections is alarming in both the pre- and post-
COVID period. Due to a limited number of antifungal drugs, there are hurdles in treatment
strategies for fungal infections due to toxic potential, drug interactions, and the development
of fungal resistance. All the antifungal targets (existing and newer) and pipeline molecules
showing promise against these targets are reviewed. The objective was to predict or repurpose
phyto-based antifungal compounds based on a dual target inhibition approach (Sterol-14-α-
demethylase and HSP-90) using a case study. In pursuit of repurposing the phytochemicals as
antifungal agents, a team of researchers visited Aravalli Biodiversity Park (ABP), Delhi, India,
to collect information on available medicinal plants. From 45 plants, a total of 1149 ligands
were collected, and virtual screening was performed using Schrodinger Suite 2016 software
to get 83 hits against both the target proteins: Sterol-14-α-demethylase and HSP-90. After
analysis of docking results, ligands were selected based on their interaction against both the
target proteins and comparison with respective standard ligands (fluconazole and ganetespib).
We have selected Isocarthamidin, Quercetin and Boeravinone B based on their docking score
and binding interaction against the HSP-90 (Docking Score -9.65, -9.22 and -9.21, respectively)
and 14-α-demethylase (Docking Score -9.19, -10.76 and -9.74 respectively). The docking
protocol was validated and MM/GBSA studies depicted better stability of selected three
ligands (Isocarthamidin, Quercetin, Boeravinone B) complex as compared to standard complex.
Further, MD simulation studies were performed using the Desmond (67) software package
version 2018-4. All the findings are presented as a case study for the prediction of dual
targets for the repurposing of certain phytochemicals as antifungal agents.
