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.

Interference of Chaga mushroom terpenoids with the attachment of SARS-CoV-2; in silico perspective

“…At the same time, betulinic acid (−7.5 kcal/mol) and inonotusane C (−7.4 kcal/mol) were the best two compounds in binding the spike. On the other hand, Beta glycan, betulinic acid, and galactomannan show high affinity against the S1 (−7.4 to −8.6 kcal/mol) of the spike as reported in another prediction study [ 64 ].…”

Chaga mushroom: a super-fungus with countless facets and untapped potential

“…Yeast, mushrooms, bacteria, and algae are all sources of a dietary fiber compound called β glucan. This compound is widely recognized as a polysaccharide found in Chaga mushrooms along, with galactomannan ( Basal et al, 2021 ; Eid et al, 2021 ; Peng and Shahidi, 2022 ). Chaga contains 8.57% β -glucan (Song 2020).…”

“…More recent research by Eid et al (2021) has shed light on the impact of Chaga on the novel coronavirus (SARS-CoV-2) that has been responsible for widespread outbreaks around the globe. In this study, the S1-carboxy-terminal domain of the SARS-receptor-binding CoV-2 domain was discovered to be closely related to -glucan, galactomannan, and betulinic acid.…”

Mushrooms as future generation healthy foods

“…Indeed, the envelope S1 spike glycoprotein, the main antigen component, of coronavirus assists the entrance of the virus into the host cell. Some Chaga components specifically interact and attach with the terminal domains of the SARS-CoV-2 S-proteins, regulating its receptors and inhibiting virus entry into the host shelter cell ( 138 ).…”