Abstract
Background: Coronavirus disease 2019 (COVID-19) as a serious global health crisis leads to high mortality and morbidity. However, currently, there are no effective vaccines and treatments for COVID-19. Main protease (Mpro) and angiotensin-converting enzyme 2 (ACE2) are the best therapeutic targets of COVID-19. Objectives: The main purpose of this study is to investigate the most appropriate drug and candidate compound for proper interaction with Mpro and ACE2 to inhibit the activity of COVID-19. Methods: In this study, repurposing of approved drugs and screening of candidate compounds using molecular docking and fragment-based QSAR method were performed to discover the potential inhibitors of Mpro and ACE2. QSAR and docking calculations were performed based on the prediction of the inhibitory activities of 5-hydroxy indanone derivatives. Based on the results, an optimal structure was proposed to inhibit the activity of COVID-19. Results: Among 2629 DrugBank approved drugs, 118 were selected considering the LibDock score and absolute energy for possible drug-Mpro interactions. Furthermore, the top 40 drugs were selected based on screening the results for possible drug- Mpro interactions with AutoDock Vina. Conclusion: Finally, evaluation of the top 40 selected drugs for possible drug-ACE2 interactions with AutoDock Vina indicated that deslanoside (DB01078) can interact effectively with both Mpro and ACE2. However, prior to conducting clinical trials, further experimental validation is needed.
Highlights
Coronavirus disease 2019 (COVID-19) as a serious global health crisis leads to high mortality and morbidity
Ligand Screening for angiotensin-converting enzyme 2 (ACE2) and Main protease (Mpro) After the first virtual screening, 118 approved drugs were selected by considering the LibDock score and absolute energy
The top 40 compounds were selected based on the screening results for possible drug-Mpro interactions with AutoDock Vina
Summary
Coronavirus disease 2019 (COVID-19) as a serious global health crisis leads to high mortality and morbidity. Objectives: The main purpose of this study is to investigate the most appropriate drug and candidate compound for proper interaction with Mpro and ACE2 to inhibit the activity of COVID-19. Methods: In this study, repurposing of approved drugs and screening of candidate compounds using molecular docking and fragment-based QSAR method were performed to discover the potential inhibitors of Mpro and ACE2. Results: Among 2629 DrugBank approved drugs, 118 were selected considering the LibDock score and absolute energy for possible drug-Mpro interactions. The top 40 drugs were selected based on screening the results for possible drug- Mpro interactions with AutoDock Vina. Conclusion: evaluation of the top 40 selected drugs for possible drug-ACE2 interactions with AutoDock Vina indicated that deslanoside (DB01078) can interact effectively with both Mpro and ACE2. The main protein products of nonstructural genes are the main protease (Mpro ), RNA dependent RNA polymerase (RdRP), and papain-like protease (PLpro) [4,5]
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