Molecular mechanisms behind anti SARS-CoV-2 action of lactoferrin

TL;DR

This study investigates how lactoferrin may inhibit SARS-CoV-2 by blocking virus attachment and entry, revealing potential molecular interactions with viral proteins and host cell receptors.

Contribution

It introduces a novel molecular modeling approach to identify lactoferrin regions that could interfere with SARS-CoV-2 infection mechanisms.

Findings

Lactoferrin may bind sialic acid receptors, preventing virus attachment.

No significant interaction between lactoferrin and ACE2 receptor.

Potential competition between lactoferrin and the spike protein's binding regions.

Abstract

Despite the huge effort to contain the infection, the novel SARS-CoV-2 coronavirus has rapidly become pandemics, mainly due to its extremely high human-to-human transmission capability, and a surprisingly high viral charge of symptom-less people. While the seek of a vaccine is still ongoing, promising results have been obtained with antiviral compounds. In particular, lactoferrin is found to have beneficial effects both in preventing and soothing the infection. Here, we explore the possible molecular mechanisms with which lactoferrin interferes with SARS-CoV-2 cell invasion, preventing attachment and/or entry of the virus. To this aim, we search for possible interactions lactoferrin may have with virus structural proteins and host receptors. Representing the molecular iso-electron surface of proteins in terms of 2D-Zernike descriptors, we (i) identified putative regions on the lactoferrin surface able to bind sialic acid receptors on the host cell membrane, sheltering the cell from the virus attachment; (ii) showed that no significant shape complementarity is present between lactoferrin and the ACE2 receptor, while (iii) two high complementarity regions are found on the N- and C-terminal domains of the SARS-CoV-2 spike protein, hinting at a possible competition between lactoferrin and ACE2 for the binding to the spike protein.