Targeting SARS-CoV-2 with Chaga mushroom: An in silico study toward developing a natural antiviral compound.

ABSTRACT

The novel coronavirus (SARS-CoV-2) has caused large-scale global outbreaks and mainly mediates host cell entry through the interaction of its spike (S) protein with the human angiotensin-converting enzyme-2 (ACE-2) receptor. As there is no effective treatment for SARS-CoV-2 to date, it is imperative to explore the efficacy of new compounds that possess potential antiviral activity. In this study, we assessed the potential binding interaction of the beneficial components of Chaga mushroom, a natural anti-inflammatory and immune booster with that of the SARS-CoV-2 receptor-binding domain (RBD) using molecular docking, MD simulation, and phylogenetic analysis. Beta glycan, betulinic acid, and galactomannan constituents of Chaga mushroom exhibited strong binding interaction (-7.4 to -8.6 kcal/mol) forming multivalent hydrogen and non-polar bonds with the viral S1-carboxy-terminal domain of the RBD. Specifically, the best interacting sites for beta glycan comprised ASN-440, SER 373, TRP-436, ASN-343, and ARG 509 with average binding energy of -8.4 kcal/mol. The best interacting sites of galactomannan included ASN-437, SER 373, TRP-436, ASN-343, and ALA 344 with a mean binding energy of -7.4 kcal/mol; and the best interacting sites of betulinic acid were ASN-437, SER 373, TRP-436, PHE 342, ARG 509, and ALA 344 that strongly interacted with the S-protein (ΔG = -8.1 kcal/mol). The docking results were also compared with an S-protein binding analog, NAG and depicted similar binding affinities compared with that of the ligands (-8.67 kcal/mol). In addition, phylogenetic analysis using global isolates depicted that the current SARS-CoV-2 isolates possessed a furin cleavage site (NSPRRA) in the RBD, which was absent in the previous isolates that indicated increased efficacy of the present virus for enhanced infection through increased interaction with ACE-2. The results showed that Chaga could be an effective natural antiviral that can supplement the current anti-SARS-CoV-2 drugs.