Abstract
To predict potential drugs for COVID-19 by using molecular docking for virtual screening of drugs approved for other clinical applications. SARS-CoV-2 is the betacoronavirus responsible for the COVID-19 pandemic. It was listed as a potential global health threat by the WHO due to high mortality, high basic reproduction number, and lack of clinically approved drugs and vaccines. The genome of the virus responsible for COVID-19 has been sequenced. In addition, the three-dimensional structure of the main protease has been determined experimentally. To identify potential drugs that can be repurposed for treatment of COVID-19 by using molecular docking based virtual screening of all approved drugs. A list of drugs approved for clinical use was obtained from the SuperDRUG2 database. The structure of the target in the apo form, as well as structures of several target-ligand complexes, were obtained from RCSB PDB. The structure of SARS-CoV-2 Mpro determined from X-ray diffraction data was used as the target. Data regarding drugs in clinical trials for COVID-19 was obtained from clinicaltrials.org. Input for molecular docking based virtual screening was prepared by using Obabel and customized python, bash, and awk scripts. Molecular docking calculations were carried out with Vina and SMINA, and the docked conformations were analyzed and visualized with PLIP, Pymol, and Rasmol. Among the drugs that are being tested in clinical trials for COVID-19, Danoprevir and Darunavir were predicted to have the highest binding affinity for the Main protease (Mpro) target of SARS-CoV-2. Saquinavir and Beclabuvir were identified as the best novel candidates for COVID-19 therapy by using Virtual Screening of drugs approved for other clinical indications. Protease inhibitors approved for treatment of other viral diseases have the potential to be repurposed for treatment of COVID-19.
Highlights
COVID-19 is a highly infectious disease (Zhao et al, 2020) associated with high mortality (Hui et al, 2020; Ruy and Chun, 2020), and there are no approved drugs or vaccines for this disease (Lu, 2020; Tian et al, 2020)
The predictions of this study have a higher probability to identify drugs that will be effective against COVID-19 and provide information that can be utilized for choice of candidate drugs for in vitro, in vivo and clinical trials
It has been reported that Chloroquine phosphate shows anti COVID-19 activity (Gao et al, 2020), the results of this study indicate that Chloroquine has a low binding energy (-5.9 kcal/mol), it mechanism of action is not likely to involve inhibition of the SARS-CoV-2 Main protease (Mpro)
Summary
COVID-19 is a highly infectious disease (Zhao et al, 2020) associated with high mortality (Hui et al, 2020; Ruy and Chun, 2020), and there are no approved drugs or vaccines for this disease (Lu, 2020; Tian et al, 2020). SARS-CoV-2, the virus responsible for COVID-19, is a betacoronavirus (Chen et al, 2020). The genome of SARS-CoV-2 has been sequenced (Zhang et al, 2020; Chan et al, 2020). The genomic sequence of SARS-CoV-2 has 96% similarity to the bat-coronavirus and 76.5% identity to the SARS-CoV (Chen, 2020). There are no approved drugs or vaccines for COVID-19, a number of clinical trials are in progress (Lu, 2020). Lopinavir and Ritonavir, combined with Chinese herbal medicines, were used in preliminary clinical studies (Wang et al, 2020)
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