Abstract
Boswellic acids (BAs) have been shown to possess antiviral activity. Using bioinformatic methods, it was tested whether or not acetyl-11-keto-β-boswellic acid (AKBA), 11-keto-β-boswellic acid (KBA), β-boswellic acid (BBA), and the phosphorylated active metabolite of Remdesivir® (RGS-P3) bind to functional proteins of SARS-CoV-2, that is, the replicase polyprotein P0DTD1, the spike glycoprotein P0DTC2, and the nucleoprotein P0DTC9. Using P0DTD1, AKBA and KBA showed micromolar binding affinity to the RNA-dependent RNA polymerase (RdRp) and to the main proteinase complex M pro . Phosphorylated BAs even bond in the nanomolar range. Due to their positive and negative charges, BAs and RGS-P3 bond to corresponding negative and positive areas of the protein. BAs and RGS-P3 docked in the tunnel-like cavity of RdRp. BAs also docked into the elongated surface rim of viral M pro . In both cases, binding occurred with active site amino acids in the lower micromolecular to upper nanomolar range. KBA, BBA, and RGS-P3 also bond to P0DTC2 and P0DTC9. The binding energies for BAs were in the range of -5.8 to -6.3 kcal/mol. RGS-P3 and BAs occluded the centrally located pore of the donut-like protein structure of P0DTC9 and, in the case of P0DTC2, RGS-P3 and BAs impacted the double-wing-like protein structure. The data of this bioinformatics study clearly show that BAs bind to three functional proteins of the SARS-CoV-2 virus responsible for adhesion and replication, as does RGS-P3, a drug on the market to treat this disease. The binding effectiveness of BAs can be increased through phosphate esterification. Whether or not BAs are druggable against the SARS-CoV-2 disease remains to be established.
Keywords: RGS-P3; SARS-CoV-2; boswellic acids; functional proteins; molecular docking.
【저자키워드】 SARS-CoV-2, molecular docking., RGS-P3, boswellic acids, functional proteins, 【초록키워드】 bioinformatics, spike glycoprotein, molecular docking, SARS-CoV-2 virus, drug, antiviral activity, binding affinity, binding energy, Replication, Protein, Effectiveness, amino acids, RdRP, RNA-dependent RNA polymerase, protein structure, nucleoprotein, disease, metabolite, binding, Amino acid, active site, phosphate, SARS-CoV-2 disease, complex, M pro, market, treat, adhesion, functional protein, proteinase, positive, polyprotein, acetyl, shown, responsible, occurred, functional, phosphorylated, impacted, docked, negative and positive, the SARS-CoV-2, the SARS-CoV-2 virus, was tested, 【제목키워드】 Bioinformatic, functional protein, the SARS-CoV-2,