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Article

Molecular Profiling of Neprilysin Expression and its Interactions with SARS-CoV-2 Spike Proteins to Develop Evidence Base Pharmacological Approaches for Therapeutic Intervention

Arun HS Kumar1★★ Corresponding author

  1. 1School of Veterinary Medicine, Univer- sity College Dublin, Belfield, Dublin, IRELAND.

CORRESPONDENCE

Arun HS Kumar

School of Veterinary Medicine, Univer- sity College Dublin, Belfield, Dublin, IRELAND.

arun.kumar@ucd.ie

Received: 10-04-2021; Revised: 20-04-2021; Accepted: 24-04-2021.

Volume 7, Issue 2 · pp. 15–20 · PUBLISHED · DOI: 10.5530/bems.7.2.7

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ABSTRACT

Introduction:Neprilysin due to its peptidase activity is involved in several physiological and pathological processes. Recently our group has reported the association of neprilysin with angiotensin-converting enzyme 2 (ACE2) network proteins which facilitate the entry of SARS-CoV-2 virus. The potential role of neprilysin beyond its peptidase activity is not known. Materials and Methods: Using the established sequence analysis and molecular docking tools, this study evaluated the molecular profile of neprilysin interaction with SARS- CoV-2 virus proteins. Results:Human neprilysin protein showed a significant sequence similarity with SARS-CoV-2 spike protein, which was further confirmed by observation of considerable interaction in the molecular docking. Human neprilysin protein was also found to additionally interact with SARS-CoV-2 proteins facilitating virus replication. The potential of neprilysin inhibitors (Sacubitril and Sacubitrilat) to interfere with neprilysin and SARS-CoV-2 proteins interactions was assessed. The neprilysin inhibitors showed binding efficacy within therapeutically feasible concentration range (1 to 150 uM). Conclusion: This study while reporting a novel role of neprilysin as potential receptor for SARS-CoV-2 virus, highlights the merit in assessing clinical efficacy of neprilysin inhibitors for the management of SARS-CoV-2 infection.

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    Kumar, A. H. (). Molecular Profiling of Neprilysin Expression and its Interactions with SARS-CoV-2 Spike Proteins to Develop Evidence Base Pharmacological Approaches for Therapeutic Intervention. Biology, Engineering, Medicine and Science Reports, 7(2), 15–20. https://doi.org/10.5530/bems.7.2.7