Screening of potential inhibitors of COVID-19 with repurposing approach via molecular docking

Abstract

is the causative organism for a pandemic disease with a high rate of infectivity and mortality. In this study, we aimed to assess the affinity between several available small molecule and proteins, including Abl kinase inhibitors, Janus kinase inhibitor, dipeptidyl peptidase 4 inhibitors, RNA-dependent RNA polymerase inhibitors, and Papainlike protease inhibitors, using binding simulation, to test whether they may be effective in inhibiting COVID-19 infection through several mechanisms. The efficiency of inhibitors was evaluated based on docking scores using AutoDock Vina software. Strong ligand-protein interactions were predicted among some of these drugs, that included: Imatinib, Remdesivir, and Telaprevir, and this may render these compounds promising candidates. Some candidate drugs might be efficient in disease control as potential inhibitors or lead compounds against the SARS-CoV-2. It is also worth highlighting the powerful immunomodulatory role of other drugs, such as Abivertinib that inhibits pro-inflammatory cytokine production associated with cytokine release syndrome (CRS) and the progression of COVID-19 infection. The potential role of other Abl kinase inhibitors, including Imatinib in reducing SARS-CoV and MERS-CoV viral titers, immune regulatory function and the development of acute respiratory distress syndrome (ARDS), indicate that this drug may be useful for COVID-19, as the SARS-CoV-2 genome is similar to SARS-CoV.

Molecular Docking Analysis of Christanoate and Christene from Christia vespertilionis Plants as Potential Inhibitors of Covid-19

“…The protein is comprised of several domains, including the N-terminal domain (1-397), finger domain (397-581 and 629-687), the palm region (582-628 and 688-815) and the thumb region (816-596) (27). The docking analysis revealed that christanoate has a higher affinity towards the active residues, which is similar to Remdesivir reported by Alizadehmohajer et al, (26) involving Lys47, His133, Asp135, Ala706, Ser709, Thr710, Gly774, Lys780 and Ser784 via hydrophobic contact in christanoate. Their study mentioned that the residues interacted with would establish an environment cohesive and stable upon forming the complex.…”

“…The primary protein catalyzes the viral RNA replication and transcription process. Therefore, inhibiting this enzyme will suppress viral replication and further infection (26). The protein is comprised of several domains, including the N-terminal domain (1-397), finger domain (397-581 and 629-687), the palm region (582-628 and 688-815) and the thumb region (816-596) (27).…”

Small molecules in the treatment of COVID-19

“…Another pyrrolopyrimidine analog, abivertinib, was found to depress cytokine production in patients with COVID-19. 323 Several pyrimidine analogs have also been found to combat SARS-CoV-2. For example, according to a recent study conducted by Huntington et al, GLPG-0187, which bears a pyrimidin ring, effectively blocked SARS-CoV-2 pseudovirus infection across multiple viral variants, especially the Omicron and Delta pseudovirus variants, in a dose-dependent manner.…”

Constructing a Novel E-Learning Course, Educational Computational Chemistry through Instructional Design Approach in the TPASK Framework

“…This process involves the prediction of ligand conformation and orientation within a specific binding site, involving algorithms and scoring functions that allow predicting biological activity by evaluating interactions between compounds and potential targets [91]. Both Autodock4 and its graphical interface, AutoDockTools, are available as free and open source software for Microsoft Windows, Mac OS, and Linux systems, Although there is ample evidence of the use of Autodock4 in the search for and development of potential drugs against Cancer, HIV, and COVID-19, among other diseases [92][93][94][95][96][97], its use has also been reported in the training of students in areas related to medicine, bioinformatics, and education [10,[98][99][100].…”