Разработка лекарств: открытый доступ
Открытый доступ
ISSN: 2169-0138
ISSN: 2169-0138
Arya Duncan, Juchara Margetson, Jada Roberts, Taquanna Baron, Neelam Buxani
The Covid-19 pandemic with 74,299,042 confirmed cases including 1,669,982 deaths, reported worldwide by WHO (accessed 1:21 PM EST on 12/20/2020) is one of the most challenging situations the humankind is facing currently. Though some vaccines to treat this catastrophic disease have been developed on fast track, but still exploring the more potential alternative therapies is need of the hour. In search of new drug candidates to treat this pandemic, a structure based virtual screening study was carried out on the 125 compounds isolated from the native Caribbean medicinal plants like Aloe vera, Lemon grass, Moringa Olifera, and Lignum vitae, to determine their inhibitory potential against three main drug targets of SARS CoV-2; main protease (PDB ID: 6LZE), nsp 15 (PDB ID: 6WLC), and RNA-dependent RNA Polymerase (PDB ID: 7BV2) of SARS-CoV-2. The virtual screening workflow was performed using Schrodinger small molecule drug discover suite, in that compounds were prepared and docked in active sites of all three proteins. The co-crystallized ligand of every protein was used as a positive control and all docking scores were compared with it. Out of 125 compounds, 37 showed favorable docking interaction with the proteins compared to the native ligand. 13 compounds showed excellent docking score against 6LZE, out of that the most negative docking score (-11.962) was of rutin in compare to native ligand (-8.095), and it also showed more negative Prime MMGBSA binding energy-70.54 kcal/mol. In case of 7BV2, 35 compounds showed better docking results than the native ramdesivir (-4.566), docking score (-8.194) of vicenin-2 was best, it also exhibited almost same binding energy of complex (-44.54 Kcal/mol) as ramdesivir. In case of 6 WLC, in site 1, orientin showed most negative dockings core (-10.896), while in site 2 swertiajaponin’s docking score is-12.364. Pharmacokinetic (ADME) properties of 37 compounds were also calculated to ascertain the druglikeness of potential inhibitors. This study provides some lead molecules that might be helpful in designing drug for treating corona virus disease.