Arch Biochem Biophys . Pharmacoinformatics approach based identification of potential Nsp15 endoribonuclease modulators for SARS-CoV-2 inhibition

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Arch Biochem Biophys


. 2021 Jan 21;108771.
doi: 10.1016/j.abb.2021.108771. Online ahead of print.
Pharmacoinformatics approach based identification of potential Nsp15 endoribonuclease modulators for SARS-CoV-2 inhibition


Rutuja Umesh Savale ¹ , Shovonlal Bhowmick ² , Sameh Mohamed Osman ³ , Fatmah Ali Alasmary ⁴ , Tahani Mazyad Almutairi ⁴ , Dalal Saied Abdullah ⁴ , Pritee Chunarkar Patil ¹ , Md Ataul Islam ⁵



Affiliations

• PMID: 33485847
• DOI: 10.1016/j.abb.2021.108771

Abstract

In the current study, a structure-based virtual screening paradigm was used to screen a small molecular database against the Non-structural protein 15 (Nsp15) endoribonuclease of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). The SARS-CoV-2 is the causative agent of the recent outbreak of coronavirus disease 2019 (COVID-19) which left the entire world locked down inside the home. A multi-step molecular docking study was performed against antiviral specific compounds (∼8722) collected from the Asinex antiviral database. The less or non-interacting molecules were wiped out sequentially in docking. Further, MM-GBSA based binding energy was estimated for 26 compounds which shows a high affinity towards the Nsp15. Further, the drug-likeness and pharmacokinetic parameters were explored, and five molecules were found to have an acceptable pharmacokinetic profile. Overall, the Glide-XP docking score and Prime-MM-GBSA binding free energy of the selected molecules were explained strong interaction potentiality towards the Nsp15 endoribonuclease. The dynamic behavior of each molecule with Nsp15 was assessed using conventional molecular dynamics (MD) simulation. The MD simulation information was strongly favors the Nsp15 and identified ligand stability. Finally, from the MD simulation trajectories, the binding free energy was estimated using the MM-PBSA method. Hence, the proposed final five molecules might be considered as potential Nsp15 modulators for SARS-CoV-2 inhibition.

Keywords: COVID-19; Molecular dynamics; Nsp15 endoribonuclease; SARS-CoV-2; Virtual screening.