Design of novel pyrimidine based remdesivir analogues with dual target specificity for SARS CoV-2: A computational approach

As the world undergone unpreceded time of tragedy with the corona virus, many researchers have raised to showcase their scientific contributions in terms of novel configured anti-viral drugs until now. Herein, we designed pyrimidine based nucleotides and assessed for the binding capability with SARS-CoV-2 viral replication targets of nsp12 RNA-dependent RNA polymerase and Mpro main protease. Molecular docking studies showed all the designed compounds to possess good binding affinity, with a few compounds which outperforms the control drug remdesivir GS-5743 and its active form GS-441524. Further molecular dynamics simulation studies confirmed their stability and preservation of the non-covalent interactions. Based on the present findings Ligand2-BzV_0Tyr, ligand3-BzV_0Ura, and ligand5-EeV_0Tyr showed good binding affinity with Mpro, whereas, ligand1-BzV_0Cys and Ligand2-BzV_0Tyr showed good binding affinity with RdRp, thus could act as potential lead compounds against SARS-CoV-2, which needs further validation studies. In particular, Ligand2-BzV_0Tyr could be more beneficial candidate with the dual target specificity for Mpro and RdRp.

Automated summary

In response to the pandemic crisis caused by the corona virus, researchers have designed pyrimidine-based nucleotides to target the replication targets of SARS-CoV-2. Molecular docking studies indicated that these compounds have good binding affinity, with some outperforming the control drug remdesivir. Molecular dynamics simulation studies further confirmed their stability and non-covalent interactions. Ligand2-BzV_0Tyr showed promising results as it exhibited dual target specificity for both Mpro and RdRp.