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In silico identification of potential phytochemical inhibitors for mpox virus: molecular docking, MD simulation, and ADMET studies

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Abstract

The mpox virus (MPXV), a member of the Poxviridae family, which recently appeared outside of the African continent has emerged as a global threat to public health. Given the scarcity of antiviral treatments for mpox disease, there is a pressing need to identify and develop new therapeutics. We investigated 5715 phytochemicals from 266 species available in IMMPAT database as potential inhibitors for six MPXV targets namely thymidylate kinase (A48R), DNA ligase (A50R), rifampicin resistance protein (D13L), palmytilated EEV membrane protein (F13L), viral core cysteine proteinase (I7L), and DNA polymerase (E9L) using molecular docking. The best-performing phytochemicals were also subjected to molecular dynamics (MD) simulations and in silico ADMET analysis. The top phytochemicals were forsythiaside for A48R, ruberythric acid for A50R, theasinensin F for D13L, theasinensin A for F13L, isocinchophyllamine for I7L, and terchebin for E9L. Interestingly, the binding energies of these potential phytochemical inhibitors were far lower than brincidofovir and tecovirimat, the standard drugs used against MPXV, hinting at better binding properties of the former. These findings may pave the way for developing new MPXV inhibitors based on natural product scaffolds. However, they must be further studied to establish their inhibitory efficacy and toxicity in in vitro and in vivo models.

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Data availability

The sequence data used in this work were obtained from NCBI. The relevant derived data are given in the supplemental tables.

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Acknowledgements

This work did not receive any specific funding.

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Author notes

  1. Larina Pinto and Shivakiran Alva have contributed equally to this work.

Authors and Affiliations

  1. Center for Bioinformatics, NITTE Deemed to be University, Mangaluru, 575018, India

    Sudeep D. Ghate, Larina Pinto, Shivakiran Alva & R. Shyama Prasad Rao

  2. Central Research Laboratory, KS Hegde Medical Academy, NITTE Deemed to be University, Mangaluru, 575018, India

    Sudeep D. Ghate & R. Shyama Prasad Rao

  3. Department of Pharmaceutical Chemistry, Nitte (Deemed to be University) NGSM Institute of Pharmaceutical Sciences (NGSMIPS), Mangaluru, 575018, India

    Mahendra Gowdru Srinivasa & B. C. Revanasiddappa

  4. Institute for Applied Research and Innovation, Neuome Technologies Pvt. Ltd., Bangalore Bioinnovation Centre, IBAB Campus, Electronic City Phase 1, Bangalore, 560100, India

    Rajani Kanth Vangala

  5. Department of Biosciences, Mangalore University, Mangaluru, 574199, India

    Prashantha Naik

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  1. Sudeep D. Ghate
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Contributions

SDG and RSPR planned the work. LP, SA, and SDG performed the work and along with RSPR wrote the manuscript. MGS helped in data curation. RBC helped in interpreting the results and gave critical inputs. RKV and PN gave inputs on phytochemicals and drug discovery. All authors contributed intellectually and edited/reviewed the manuscript. All authors have read and agreed to the published version of the manuscript.

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Correspondence to Sudeep D. Ghate or R. Shyama Prasad Rao.

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Ghate, S.D., Pinto, L., Alva, S. et al. In silico identification of potential phytochemical inhibitors for mpox virus: molecular docking, MD simulation, and ADMET studies. Mol Divers (2024). https://doi.org/10.1007/s11030-023-10797-2

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