In silico investigation of potential inhibitors to main protease and spike protein of SARS-CoV-2 in propolis
Azza Hanif Harisna, Rizky Nurdiansyah, Putri Hawa Syaifie, Dwi Nugroho, Kurniawan Eko Saputro, Firdayani Firdayani, Chandra Dwi Prakoso, Nurul Taufiqu Rochman, Nurwenda Novan Maulana, Alfian Noviyanto, Etik Mardliyati
Abstract
Docking analysis of propolis's natural compound was successfully performed against SARS-CoV-2 main protease (Mpro) and spike protein subunit 2 (S2). Initially, the propolis's protein was screened using chromatography analysis and successfully identified 22 compounds in the propolis. Four compounds were further investigated, i.e., neoblavaisoflavone, methylophiopogonone A, 3'-Methoxydaidzin, and genistin. The binding affinity of 3'-Methoxydaidzin was -7.7 kcal/mol, which is similar to nelfinavir (control), while the others were -7.6 kcal/mol. However, we found the key residue of Glu A:166 in the methylophiopogonone A and genistin, even though the predicted binding energy slightly higher than nelfinavir. In contrast, the predicted binding affinity of neoblavaisoflavone, methylophiopogonone A, 3'-Methoxydaidzin, and genistin against S2 were -8.1, -8.2, -8.3, and -8.3 kcal/mol, respectively, which is far below of the control (pravastatin, -7.3 kcal/mol). Instead of conventional hydrogen bonding, the π bonding influenced the binding affinity against S2. The results reveal that this is the first report about methylophiopogonone A, 3'-Methoxydaidzin, and genistin as candidates for anti-viral agents. Those compounds can then be further explored and used as a parent backbone molecule to develop a new supplementation for preventing SARS-CoV-2 infections during COVID-19 outbreaks.