Molecular docking and ADMET study of bioactive compounds of Glycyrrhiza glabra against main protease of SARS-CoV2

Abstract

Recent pandemic situation of COVID-19 is caused due to SARS-CoV2 and almost all the countries of the world has been affected by this highly contagious virus. Main protease (M pro ) of this virus is a highly attractive drug target among various other enzymes due to its ability to process poly-protein that is the translated product of the SARS-CoV2 RNA. The aim of the present study demonstrates molecular docking study of Glycyrrhiza glabra (Gg) active compounds such as Glycyrrhizic acid (GA), Liquiritigenin (L) and Glabridin (G) against the M pro . Docking studies shows that these active compounds bind strongly with some of the amino acid residues in the active site of M pro and inhibits the enzyme strongly. GA, L, and G are proposed to be strong inhibitors of the enzyme and the amino acids: His 41 , Gly 143 , Gln 189 , Glu 166 , Cys 145 , Thr 25 , Asn 142 , Met 49 , Cys 44 , Thr 45 and pro 168 present in the active site of M pro were shown to make non-covalent interaction with these compounds. In silico ADMET properties prediction also shows that Gg active compounds had good solubility, absorption, permeation, non-toxic, and non- carcinogenic characteristics. Our finding concludes that all of the three active compounds of Gg could have the potential to be strong inhibitors for M pro of SARS-CoV2 but glycyrrhizic acid have a high binding affinity of -8.0 Kcal/mol and glycyrrhizic acid have good ADMET properties than the other two.

Molecular docking, binding mode analysis, molecular dynamics, and prediction of ADMET/toxicity properties of selective potential antiviral agents against SARS-CoV-2 main protease: an effort toward drug repurposing to combat COVID-19

“…Recently in 2020, Nguyen et al [50] also unveiled the fact that Gly143, Cys145, Glu166, and His163 of M pro are the region to form a hydrogen bond and highly favorable molecular fragments for the development of novel SARS-CoV-2 main protease inhibitors, which resembles the finding in the current study. An in silico study performed by Srivastava et al demonstrates the binding stability of Glycyrrhiza glabra derivatives, i.e., GA as bioactive inhibitor inside the SARS-CoV-2 M pro and proposed HIS41, GLY143, GLN189, GLU166, CYS145, THR25, ASN142, MET49, and PRO168 present in the active site of M pro were shown to make non-covalent interaction with the target compound, which was found consistent with our observation [51].…”

Glycyrrhizin Effectively Inhibits SARS-CoV-2 Replication by Inhibiting the Viral Main Protease

“…Next, we investigated the underlying mechanism of how glycyrrhizin may interfere with the virus replication. Recently, protease inhibitory activity of glycyrrhizin was predicted using in silico simulations [ 8 ]. The SARS-CoV-2 main protease M pro , also known as the 3CL protease, plays a vital role in processing the viral polyproteins that are translated from SARS-CoV-2 RNA.…”

“…Glycyrrhizin was discussed in in silico simulations as a potential protease inhibitor [ 8 , 9 ]. Beside the viral main protease (M pro ), the human transmembrane serine protease (TMPRSS2) is another discussed target of glycyrrhizin.…”

Phytotherapy for treatment of cytokine storm in COVID-19

“…Further, a study demonstrated that GA, Liquiritigenin (L) and Glabridin (G) active compounds of Glycyrrhiza glabra inhibits the enzymatic activity of M pro by binding strongly to the active site. But in comparison to other two compounds GA showed higher binding affinity of -8.0 Kcal/mol [96]. Also, GA could be considered as the best molecule of Glycyrrhiza glabra that could be useful against SARS-CoV-2 [97].…”