Characterization of the NiRAN domain from RNA-dependent RNA polymerase provides insights into a potential therapeutic target against SARS-CoV-2
Fig 6
Impeding the activity of the SARS-CoV-2 RdRp NiRAN domain reduces viral load in infected cells.
(A) While treatment with all the kinase inhibitors abrogate the kinase like activity of CoV-2 RdRp, the activity human Akt2 is majorly inhibited by Sorafenib and SU6656 with Sunitinib only exhibiting mild inhibition. (B) Treatment of CoV2-RdRp with nucleotidyl transferase inhibitors 135659024, 122108 and 65482 exhibit conspicuous inhibition of the kinase activity in micromolar concentrations. The compound 4534 however fails to exhibit any inhibitory potential. (C) 5 μM Sorafenib effectively reduces viral replication in SARS-CoV-2 infected Vero E6 cells. In addition, a combination of Sorafenib with 1 μM Remdesivir completely neutralizes SARS-CoV-2 as evident by a Ct value similar to that of uninfected cells (The bars represent mean and standard error. The symbols “*” and “**” represent significance for p-value less than 0.05 and 0.005, respectively. The symbol “ns” represents non-significance).