Drug Repurposing of Lactoferrin Combination in a Nanodrug Delivery System to Combat Severe Acute Respiratory Syndrome Coronavirus-2 Infection

Authors

Assem Barakat^{1, 2, *,} , Abdullah Mohammed Al-Majid^1, , Gehad Lotfy^3, , Mohamed Ali^1, , Ahmed Mostafa^4, , Yaseen A.M.M. Elshaier^5,

¹Department of Chemistry, College of Science, King Saud University, Riyadh, Saudi Arabia

²Department of Chemistry, Faculty of Science, Alexandria University, Ibrahimia, Alexandria, Egypt

³Department of Pharmacy, Aldara Hospital and Medical Center, Al Maazer, Riyadh, Saudi Arabia

⁴Center of Scientific Excellence for Influenza Viruses, National Research Centre, Giza, Egypt

⁵Department of Organic and Medicinal Chemistry, Faculty of Pharmacy, University of Sadat City, Menoufiya, Egypt

^*Corresponding author. Email: ambarakat@ksu.edu.sa

DOI

10.2991/dsahmj.k.210810.001How to use a DOI?

Keywords

Drug repurposing; nanodrug delivery system; lactoferrin; nitazoxanide; spirooxindole; molecular modeling; SARS-CoV-2; COVID-19

Abstract

A drug repurposing approach for Food and Drug Administration (FDA)-approved drugs and preclinical entity by using cheminformatics and chemical transformational method, with the objective of discovering safer novel potent inhibitors that are selective for COVID-19, is reported. We examined the action of lactoferrin against Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). Lactoferrin was tested not only as therapy but also as a nanocarrier. Among the different repurposed drugs approved to help control the COVID-19 pandemic, we focused on nitazoxanide in a nanodrug delivery form. Lactoferrin activity improved after it was used in combination with nitazoxanide [half-maximal inhibitory concentration (IC₅₀) = 2.72, 1.34 with Selectivity Index (SI) = 25 and 32, respectively]. These results will help us enhance the activity of lactoferrin as a nanocarrier for a variety of selected drugs. In addition, the antiviral activity of the spirooxindole scaffold showed interesting results against SARS-CoV-2 as well as Middle East respiratory syndrome (MERS)-CoV with an IC₅₀ of 0.03 and 0.001 mM, respectively. The molecular modeling study revealed that nitazoxanide has a high similarity to arbidol. Docking outputs emphasize the importance of anilide functionality in drug activity because of its ability to form essential HB main protease and spike protein active sites. By understanding the binding mode, these data will help us design new bioactive drug candidates against SARS-CoV-2.

Copyright

© 2021 Dr. Sulaiman Al Habib Medical Group. Publishing services by Atlantis Press International B.V.

Open Access

This is an open access article distributed under the CC BY-NC 4.0 license (http://creativecommons.org/licenses/by-nc/4.0/).

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TY  - JOUR
AU  - Assem Barakat
AU  - Abdullah Mohammed Al-Majid
AU  - Gehad Lotfy
AU  - Mohamed Ali
AU  - Ahmed Mostafa
AU  - Yaseen A.M.M. Elshaier
PY  - 2021
DA  - 2021/08/16
TI  - Drug Repurposing of Lactoferrin Combination in a Nanodrug Delivery System to Combat Severe Acute Respiratory Syndrome Coronavirus-2 Infection
JO  - Dr. Sulaiman Al Habib Medical Journal
SP  - 104
EP  - 112
VL  - 3
IS  - 3
SN  - 2590-3349
UR  - https://doi.org/10.2991/dsahmj.k.210810.001
DO  - 10.2991/dsahmj.k.210810.001
ID  - Barakat2021
ER  -