In-silico prediction of highly promising natural fungicides against the destructive blast fungus Magnaporthe oryzae

Md Abdullah Al Mamun Khan; Asif Ahsan; Md Arif Khan; Jannatul Maowa Sanjana; Suvro Biswas; Md Abu Saleh; Dipali Rani Gupta; M Nazmul Hoque; Tahsin Islam Sakif; Md Masuder Rahman; Tofazzal Islam

doi:10.1016/j.heliyon.2023.e15113

In-silico prediction of highly promising natural fungicides against the destructive blast fungus Magnaporthe oryzae

Heliyon. 2023 Apr 10;9(4):e15113. doi: 10.1016/j.heliyon.2023.e15113. eCollection 2023 Apr.

Authors

Affiliations

¹ Department of Biotechnology and Genetic Engineering, Mawlana Bhashani Science and Technology University, Tangail 1902, Bangladesh.
² Department of Biotechnology, Bangladesh Agricultural University, Mymensingh, 2202, Bangladesh.
³ Department of Biotechnology and Genetic Engineering, University of Development Alternative, Dhaka 1209, Bangladesh.
⁴ Bio-Bio-1 Bioinformatics Research Foundation, Dhaka, Bangladesh.
⁵ Microbiology Laboratory, Department of Genetic Engineering and Biotechnology, University of Rajshahi, Rajshahi 6205, Bangladesh.
⁶ Institute of Biotechnology and Genetic Engineering (IBGE), Bangabandhu Sheikh Mujibur Rahman Agricultural University (BSMRAU), Gazipur 1706, Bangladesh.
⁷ Department of Gynecology, Obstetrics and Reproductive Health, BSMRAU, Gazipur 1706, Bangladesh.
⁸ Lane Department of Computer Science and Electrical Engineering, West Virginia University, Morgantown, WV 26506-6109, USA.

Abstract

Magnaporthe oryzae causes destructive blast disease in more than 50 species of the major cereal crops rice, wheat and maize and destroys food of millions of people worldwide. Application of synthetic chemical fungicides are environmentally hazardous and unreliable in controlling M. oryzae. Conversely, naturally occurring biofungicides with multiple modes of actions are needed to be discovered for combatting the blast fungus. To find the effective biofungicides, we performed molecular docking study of some potential antifungal natural compounds targeting two proteins including a single-stranded DNA binding protein MoSub1 (4AGH), and an effector protein AVR-Pik (5E9G) of M. oryzae that regulates transcription in fungus and/or suppresses the host cell immunity. The thirty-nine natural compounds previously shown to inhibit M. oryzae growth and reproduction were put under molecular docking against these two proteins followed by simulation, free energy, and interaction analysis of protein-ligand complexes. The virtual screening revealed that two alkaloidal metabolites, camptothecin and GKK1032A2 showed excellent binding energy with any of these target proteins compared to reference commercial fungicides, azoxystrobin and strobilurin. Of the detected compounds, GKK1032A2 bound to both target proteins of M. oryzae. Both compounds showed excellent bioactivity scores as compared to the reference fungicides. Results of our computational biological study suggest that both camptothecin and GKK1032A2 are potential fungicides that could also be considered as lead compounds to design novel fungicides against the blast fungus. Furthermore, the GKK1032A2 acted as a multi-site mode of action fungicide against M. oryzae.

Keywords: Antifungal metabolites; Magnaporthe oryzae; Molecular docking; Protein; ssDNA.