Abstract
Galectin-3 is a carbohydrate-binding protein and the most studied member of the galectin family. It regulates several functions throughout the body, among which are inflammation and post-injury remodelling. Recent studies have highlighted the similarity between Galectin-3′s carbohydrate recognition domain and the so-called “galectin fold” present on the N-terminal domain of the S1 sub-unit of the SARS-CoV-2 spike protein. Sialic acids binding to the N-terminal domain of the Spike protein are known to be crucial for viral entry into humans, and the role of Galectin-3 as a mediator of lung fibrosis has long been the object of study since its levels have been found to be abnormally high in alveolar macrophages following lung injury. In this context, the discovery of a double inhibitor may both prevent viral entry and reduce post-infection pulmonary fibrosis. In this study, we use a database of 56 compounds, among which 37 have known experimental affinity with Galectin-3. We carry out virtual screening of this database with respect to Galectin-3 and Spike protein. Several ligands are found to exhibit promising binding affinity and interaction with the Spike protein’s N-terminal domain as well as with Galectin-3. This finding strongly suggests that existing Galectin-3 inhibitors possess dual-binding capabilities to disrupt Spike–ACE2 interactions. Herein we identify the most promising inhibitors of Galectin-3 and Spike proteins, of which five emerge as potential dual effective inhibitors. Our preliminary results warrant further in vitro and in vivo testing of these putative inhibitors against SARS-CoV-2 with the hope of being able to halt the spread of the virus in the future.
Highlights
As experimental pKd values were only available for the Galectin-3 protein in the literature, we only performed regression analysis to evaluate the correlation between the obtained docking scores and experimental pKd values for six different protein structures available in Protein Data Bank
Gal-3 and spike dual inhibitors have the same contacts as the top-ranked inhibitors with the exception that L18 and L100 contacts are missing in Gal-3 protein
The main idea of the study described was to find a dual inhibitor of both Gal-3 and the severe acute respiratory syndrome (SARS)-CoV2 S1 - N-terminal domain (NTD) that could reduce the release of cytokines and prevent viral attachment to host cells
Summary
The COVID-19 pandemic is a worldwide emergency, as its rapid spread and high mortality rate have caused severe challenges. On 30 January 2020, the World Health. Organization declared the SARS-CoV-2 epidemic a public health emergency of international concern [1]. The number of people infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV2), the causative agent of COVID-19, has been steadily increasing worldwide [2]. SARS-CoV-2 is an enveloped non-segmented positive-sense RNA β-coronavirus belonging to the same family as the severe acute respiratory syndrome (SARS) and Middle East Respiratory Syndrome (MERS) viruses [3].
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