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

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 (IC 50 ) = 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 IC 50 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.