I.F.D. Faratisha, A.W. Cahyono, N.E. Erwan, A.M. Putri, D.G. Ariel, K.C. Yunita, R.Y.B. Nugraha, K. Mardhiyyah, L.E. Fitri
Background: Malaria is a constantly challenging problem, notably in the Coronavirus Disease-19 (COVID-19) pandemic. The syndemic condition, malaria-COVID-19 co-infections, had been reported. Our previous study successfully revealed several compounds from Streptomyces hygroscopicus subsp. Hygroscopicus, including nigericin that has both antimalarial and antiviral effects. In malaria infection, Plasmodium falciparum Chloroquine Resistance Transporter (PfCRT) is the potential target for eliminating Plasmodium. Meanwhile, for SARS-CoV-2 infection, MPro is an essential protein for SARS-CoV-2 survival. This research aims to examine the potential effect of nigericin towards Plasmodium and SARS-CoV-2 by assessing its molecular interaction with PfCRT and MPro through molecular docking study. Methods: The protein target PfCRT and MPro were obtained from Protein Data Bank. Nigericin and the control ligand (chloroquine and N3) were obtained from PubChem. The pharmacokinetic analysis was done using SwissADME. Specific molecular docking was conducted using PyRx 0.9 and was visualized using LigPlot and PyMOL. Results: Nigericin has a large molecular weight, leading to the non-fulfillment of the Lipinski rule for oral administration. Through molecular docking study, the binding affinity of the Nigericin-PfCRT complex was -8.1 kcal/mol, and Nigericin-MPro was -8.6 kcal/mol. These binding affinities were stronger than the control ligand. The interaction between Nigericin-PfCRT and Nigericin-MPro share a similar pocket-site and amino acid residues as the control ligands. Conclusion: Nigericin has potential antimalarial and anti-coronavirus effects through molecular docking perspective by assessing the binding affinity and similarity of amino acid residues compared to control. Administration of systemic route can be an option in giving nigericin. © 2022 Phcogj.Com. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.
Malaria Research Group, Faculty of Medicine, Universitas Brawijaya, East Java, Malang, 65145, Indonesia; Doctoral Program in Medical Science, Faculty of Medicine, Universitas Brawijaya, East Java, Malang, 65145, Indonesia; Master Program in Biomedical Science, Faculty of Medicine, Universitas Brawijaya, East Java, Malang, 65145, Indonesia; Department of Parasitology, Faculty of Medicine, Universitas Brawijaya, East Java, Malang, 65145, Indonesia; Department of Biochemistry & Biomolecula Faculty of Medicine, Universitas Brawijaya, East Java, Malang, 65145, Indonesia