Abstract
Simple SummaryWith the urgent necessity of potential treatment against novel coronavirus disease, we used several computational methods to search for active drugs from an extensive database. The results of our investigation suggested several established drugs that can be subjected to further analysis for the treatment of novel coronavirus disease. Various methods used in this study proved the effectiveness of the retrieved drugs. Therefore, our findings highly recommend the mentioned drugs to be scrutinized to discover drugs against novel coronavirus.Novel coronavirus disease (COVID-19) was identified from China in December 2019 and spread rapidly through human-to-human transmission, affecting so many people worldwide. Until now, there has been no specific treatment against the disease and repurposing of the drug. Our investigation aimed to screen potential inhibitors against coronavirus for the repurposing of drugs. Our study analyzed sequence comparison among SARS-CoV, SARS-CoV-2, and MERS-CoV to determine the identity matrix using discovery studio. SARS-CoV-2 Mpro was targeted to generate an E-pharmacophore hypothesis to screen drugs from the DrugBank database having similar features. Promising drugs were used for docking-based virtual screening at several precisions. Best hits from virtual screening were subjected to MM/GBSA analysis to evaluate binding free energy, followed by the analysis of binding interactions. Furthermore, the molecular dynamics simulation approaches were carried out to assess the docked complex’s conformational stability. A total of 33 drug classes were found from virtual screening based on their docking scores. Among them, seven potential drugs with several anticancer, antibiotic, and immunometabolic categories were screened and showed promising MM/GBSA scores. During interaction analysis, these drugs exhibited different types of hydrogen and hydrophobic interactions with amino acid residue. Besides, 17 experimental drugs selected from virtual screening might be crucial for drug discovery against COVID-19. The RMSD, RMSF, SASA, Rg, and MM/PBSA descriptors from molecular dynamics simulation confirmed the complex’s firm nature. Seven promising drugs for repurposing against SARS-CoV-2 main protease (Mpro), namely sapanisertib, ornidazole, napabucasin, lenalidomide, daniquidone, indoximod, and salicylamide, could be vital for the treatment of COVID-19. However, extensive in vivo and in vitro studies are required to evaluate the mentioned drug’s activity.
Highlights
Novel coronavirus disease (COVID-19) has become a threatening illness globally and was declared as a pandemic by WHO (World Health Organization)
The coronavirus β (β-CoV) group is divided into severe acute respiratory syndrome coronavirus (SARS-CoV), severe acute respiratory syndrome coronavirus-2 (SARSCoV-2), and middle east respiratory syndrome coronavirus (MERS-CoV) [3]
The aim of our study was to focus on the SARS-CoV-2 main protease as a potential drug target to screen drugs for repurposing against COVID-19
Summary
Novel coronavirus disease (COVID-19) has become a threatening illness globally and was declared as a pandemic by WHO (World Health Organization). The coronavirus β (β-CoV) group is divided into severe acute respiratory syndrome coronavirus (SARS-CoV), severe acute respiratory syndrome coronavirus-2 (SARSCoV-2), and middle east respiratory syndrome coronavirus (MERS-CoV) [3]. These three types of virus are highly fatal and responsible for respiratory, liver, gastrointestinal, and central nervous system damage in humans and animals [4]. In case of respiratory disease, it can lead to severe pneumonia with several symptoms, including fever, dry cough, vomiting, fatigue, diarrhea, and shortness of breath [5,6]
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