Targeting SARS-COV-2 non-structural protein 16: a virtual drug repurposing study

Abstract

Non-Structural Protein 16 (nsp-16), a viral RNA methyltransferase (MTase), is one of the highly viable targets for drug discovery of coronaviruses including SARS-CoV-2. In this study, drug discovery of SARS-CoV-2 nsp-16 has been performed by a virtual drug repurposing approach. First, drug shapebased screening (among FDA approved drugs) with a known template of MTase inhibitor, sinefungin was done and best compounds with high similarity scores were selected. In addition to the selected compounds, 4 nucleoside analogs of anti-viral (Raltgravir, Maraviroc and Favipiravir) and anti-inflammatory (Prednisolone) drugs were selected for further investigations. Then, binding energies and interaction modes were found by molecular docking approaches and compouds with lower energy were selected for further investigation. After that, Molecular dynamics (MD) simulation was carried to test the potential selected compounds in a realistic environment. The results showed that Raltegravir and Maraviroc among other compounds can bind strongly to the active site of the protein compared to sinefungin, and can be potential candidates to inhibit NSP-16. Also, the MD simulation results suggested that the Maraviroc and Raltegravir are more effective drug candidates than Sinefungin for inhibiting the enzyme. It is concluded that Raltegravir and Maraviroc which may be used in the treatment of COVID-19 after Invitro and invivo studies and clinical trial for final confirmation of drug effectiveness.

Identification of naphthyridine and quinoline derivatives as potential Nsp16-Nsp10 inhibitors: a pharmacoinformatics study

“…The above observations strongly suggested that Nsp16-Nsp10 may be a crucial drug target for highly specific anti-coronavirus drugs in comparison to the viral MTase active site (Rosas-Lemus et al, 2020). Several interesting studies have already been done by considering Nsp16-Nsp10 as an effective drug target for SARS-CoV-2 inhibition (Cavasotto & Di Filippo, 2020;Culletta et al, 2020;Kadioglu et al, 2020;Kandwal & Fayne, 2020;Tazikeh-Lemeski et al, 2020).…”

Structural analysis, virtual screening and molecular simulation to identify potential inhibitors targeting 2'-O-ribose methyltransferase of SARS-CoV-2 coronavirus

“…Moreover, in silico approaches, including molecular dynamics (MD), have also been widely used to determine the conformational space of the investigated targets, ligands, and ligandtarget complexes, and thus better understand the dynamic behavior of ligand-target complexes Pinzi & Rastelli, 2019;Rajendran et al, 2018;Slater & Kontoyianni, 2019;Sled z & Caflisch, 2018). Very recently, a virtual screening approach was used to identify potential drugs to inhibit SARS-CoV-2 proteins, including surface spike glycoprotein, main protease, and nsp16 Panda et al, 2020;Tazikeh-Lemeski et al, 2020;Vijayan et al, 2020). For example, Bhardwaj et al reported the identification of bioactive molecules from tea plant as SARS-CoV-2 main protease inhibitors .…”

“…reported the identification of bioactive molecules from tea plant as SARS-CoV-2 main protease inhibitors (Bhardwaj et al., 2020 ). Molecular docking and virtual screening approaches also have been attempted to identify compounds targeting 2′-O-MTase of SARS-CoV-2 (Encinar & Menendez, 2020 ; Hijikata et al., 2020 ; Tazikeh-Lemeski et al., 2020 ; Vijayan et al., 2020 ).…”

Repurposing drugs for treatment of SARS-CoV-2 infection: computational design insights into mechanisms of action

“…Another study focused on using DBVS to determine the inhibitory activity of FDA approved drugs against nsp16. The results indicated the potential of anti-viral drugs (maraviroc and raltegravir) and an anti-inflammatory drug (prednisolone) to be effective drug candidates against nsp16 (Tazikeh-Lemeski et al, 2020 ). Another such study integrated a data-driven repositioning framework to predict effective drug candidates with in silico screening followed by wet-lab validation.…”