Different In Silico Approaches Using Heterocyclic Derivatives against the Binding between Different Lineages of SARS-CoV-2 and ACE2.

Over the last few years, the study of the SARS-CoV-2 spike protein and its mutations has become essential in understanding how it interacts with human host receptors. Since the crystallized structure of the spike protein bound to the angiotensin-converting enzyme 2 (ACE2) receptor was released (PDB code 6M0J), in silico studies have been performed to understand the interactions between these two proteins. Specifically, in this study, heterocyclic compounds with different chemical characteristics were examined to highlight the possibility of interaction with the spike protein and the disruption of the interaction between ACE2 and the spike protein. Our results showed that these compounds interacted with the spike protein and interposed in the interaction zone with ACE2. Although further studies are needed, this work points to these heterocyclic push-pull compounds as possible agents capable of interacting with the spike protein, with the potential for the inhibition of spike protein-ACE2 binding.

Effects of Mangiferin on LPS-Induced Inflammation and SARS-CoV-2 Viral Adsorption in Human Lung Cells.

The growing interest in natural bioactive molecules, as an approach to many pathological contexts, is widely justified by the necessity to overcome the disadvantageous benefit-risk ratio related to traditional therapies. Among them, mangiferin (MGF) shows promising beneficial properties such as antioxidant, anti-inflammatory, and immunomodulatory effects. In this study, we aimed to investigate the antioxidant and anti-inflammatory properties of MGF on lipopolysaccharide (LPS)-induced lung NCI-H292 cells, focusing on its role against COVID-19 adsorption. In order to obtain this information, cells treated with LPS, with or without MGF, were analyzed performing wound healing, gene expression of inflammatory cytokines, GSH quantification, and JC-1 staining. Moreover, the inhibition of viral adsorption was evaluated microbiologically and the results were further confirmed by molecular docking analysis. In this regard, MGF downregulates the expression of several inflammatory factors, enhances GSH levels, promotes the wound healing rate, and restores the mitochondrial dysfunction caused by LPS. In addition, MGF significantly inhibits SARS-CoV-2 adsorption as shown by the gene expression of ACE2 and TMPRSS-2, and furtherly confirmed by microbiological and molecular modeling evaluation. Although more investigations are still needed, all data obtained constitute a solid background, demonstrating the cytoprotective role of MGF in inflammatory mechanisms including COVID-19 infection.