Computational drug repurposing study of antiviral drugs against main protease, RNA polymerase, and spike proteins of SARS-CoV-2 using molecular docking method.

OBJECTIVES: The new Coronavirus (SARS-CoV-2) created a pandemic in the world in late 2019 and early 2020. Unfortunately, despite the increasing prevalence of the disease, there is no effective drug for the treatment. A computational drug repurposing study would be an appropriate and rapid way to provide an effective drug in the treatment of the coronavirus disease of 2019 (COVID-19) pandemic. In this study, the inhibitory potential of more than 50 antiviral drugs on three important proteins of SARS-CoV-2, was investigated using the molecular docking method. METHODS: By literature review, three important proteins, including main protease, RNA-dependent RNA polymerase (RdRp), and spike, were selected as the drug targets. The three-dimensional (3D) structure of protease, spike, and RdRp proteins was obtained from the Protein Data Bank. Proteins were energy minimized. More than 50 antiviral drugs were considered as candidates for protein inhibition, and their 3D structure was obtained from Drug Bank. Molecular docking settings were defined using Autodock 4.2 software and the algorithm was executed. RESULTS: Based on the estimated binding energy of docking and hydrogen bond analysis and the position of drug binding, five drugs including, indinavir, lopinavir, saquinavir, nelfinavir, and remdesivir, had the highest inhibitory potential for all three proteins. CONCLUSIONS: According to the results, among the mentioned drugs, saquinavir and lopinavir showed the highest inhibitory potential for all three proteins compared to the other drugs. This study suggests that saquinavir and lopinavir could be included in the laboratory phase studies as a two-drug treatment for SARS-CoV-2 inhibition.

DMLR: A toolkit for investigation of deoxyribozyme-mediated ligation based on real time PCR.

Deoxyribozymes or DNAzyme are identified as catalytic DNA sequences which catalyze different chemical reactions. Ligating deoxyribozymes catalyze the formation of branched and linear products. Due to the lack of efficient read-out systems, there is no report on in vivo application of ligating deoxyribozymes. To expand the biological application of branched-RNA forming deoxyribozymes, we performed our study in order to suggest a practical toolkit for measurement of in vivo real-time activity of ligating deoxyribozymes. Further in vitro studies were designed to analyze the effects of the location of branch site on reverse transcriptase (RT) interference. With this toolkit even the activity of RT was measured precisely. Our results indicate that the activity of RT enzyme significantly affected by a 17 nt branched adaptor synthesized by 10DM24 ligating deoxyribozyme. The RT stalls at or near the RNA branch point during both initiation and elongation phases. The DNA synthesis is decreased 4.3 and 2.7 fold during initiation and elongation phases respectively. In conclusion, we introduce a general and practical toolkit called "DMLR" which is based on Real-time PCR method. The use of DMLR precisely determines RT behavior when encountered with any backbone modification with the ability of stopping the enzyme activity.