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Epicatechin analogues may hinder human parainfluenza virus infection by inhibition of hemagglutinin neuraminidase protein and prevention of cellular entry

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Abstract

Human parainfluenza viruses (HPIVs) are ( −)ssRNA viruses belonging to Paramyoviridaie family. They are one of the leading causes of mortality in infants and young children and can cause ailments like croup, bronchitis, and pneumonia. Currently, no antiviral medications or vaccines are available to effectively treat parainfluenza. This necessitates the search for a novel and effective treatment. Computer-aided drug design (CADD) methodology can be utilized to discover target-based inhibitors with high accuracy in less time. A library of 45 phytocompounds with immunomodulatory properties was prepared. Thereafter, molecular docking studies were conducted to characterize the binding behavior of ligand in the binding pocket of HPIV3 HN protein. The physicochemical properties for screened compounds were computed, and the top hits from docking studies were further analyzed and validated using molecular dynamics simulation studies using the Desmond module of Schrodinger Suite 2021–1, followed by MM/GBSA analysis. The compounds CID:72276 (1) and CID:107905 (2) emerged as lead compounds of our in silico investigation. Further in vitro studies will be required to prove the efficacy of lead compounds as inhibitors and to determine the exact mechanism of their inhibition.

Graphical abstract

Computational studies predict three natural flavonoids to inhibit the HN protein of HPIV3.

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Data availability

All data generated or analyzed during this study are included in this published article (and its supplementary information files).

Software availability

All the tools and databases used in this study are open source and are freely accessible on the web unless otherwise specified. Discovery Studio Visualizer 2021 is proprietary software distributed for free by BIOVIA. Schrodinger Suite 2021–1 is proprietary fee-based software distributed by Schrodinger Inc. The Desmond module of Schrodinger Suite 2021–1 is distributed free of cost by D. E. Shaw Research under the Academic License.

Abbreviations

ADME/T:

Absorption, distribution, metabolism, excretion, and toxicity

GA:

Genetic algorithm

HPIV:

Human parainfluenza virus

HN:

Hemagglutinin neuraminidase

MDSim:

Molecular dynamics simulation

MM/GBSA:

Molecular mechanics/generalized born model and solvent accessibility

RdRp:

RNA-dependent RNA polymerase

rGyr:

Radius of gyration

RMSD:

Root mean square deviation

RMSF:

Root mean square fluctuation

SASA:

Solvent accessibility surface area

ssRNA:

Single-stranded ribonucleic acid

VSGB:

Variable dielectric generalized Born solvation method

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Acknowledgements

SB is thankful to Mr. Kishore Venkatesh and Ms. Shelvia Malik of Schrodinger Inc. for providing the temporary license of Schrodinger Suite 2021-1 for PCA and MM/GBSA Analysis. SB expresses his gratitude to Mr. Rajkumar Chakraborty, Ph.D. Scholar, Delhi Technological University, for his valuable input in the process of drafting the manuscript.

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Authors and Affiliations

  1. Department of Biotechnology, Delhi Technological University, Shahbad Daulatpur, Main Bawana Rd, New Delhi, 110042, India

    Sidharth Bhasin, Megh Nadar & Yasha Hasija

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  1. Sidharth Bhasin
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  2. Megh Nadar
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  3. Yasha Hasija
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Contributions

Sidharth Bhasin: conceptualization, methodology, validation, writing — original draft preparation. Megh Nadar: data curation, investigation. Yasha Hasija: supervision, writing — review and editing.

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Correspondence to Yasha Hasija.

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Bhasin, S., Nadar, M. & Hasija, Y. Epicatechin analogues may hinder human parainfluenza virus infection by inhibition of hemagglutinin neuraminidase protein and prevention of cellular entry. J Mol Model 28, 319 (2022). https://doi.org/10.1007/s00894-022-05310-9

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