Structure-based drug repurposing for targeting Nsp9 replicase and spike proteins of severe acute respiratory syndrome coronavirus 2

Vaishali Chandel, Prem Prakash Sharma, Sibi Raj, Ramesh Choudhari, Brijesh Rathi, Dhruv Kumar

10.1080/07391102.2020.1811773

Research curated

Abstract

Drug re-purposing might be a fast and efficient way of drug development against the novel coronavirus disease 2019 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We applied a bioinformatics approach using molecular dynamics and docking to identify FDA-approved drugs that can be re-purposed to potentially inhibit the non-structural protein 9 (Nsp9) replicase and spike proteins in SARS-CoV-2. We performed virtual screening of FDA-approved compounds, including antiviral, anti-malarial, anti-parasitic, anti-fungal, anti-tuberculosis, and active phytochemicals against the Nsp9 replicase and spike proteins. Selected hit compounds were identified based on their highest binding energy and favorable absorption, distribution, metabolism and excretion (ADME) profile. Conivaptan, an arginine vasopressin antagonist drug exhibited the highest binding energy (-8.4 Kcal/mol) and maximum stability with the amino acid residues present at the active site of the Nsp9 replicase. Tegobuvir, a non-nucleoside inhibitor of the hepatitis C virus, also exhibited maximum stability along with the highest binding energy (-8.1 Kcal/mol) at the active site of the spike proteins. Molecular docking scores were further validated by molecular dynamics using Schrodinger, which supported the strong stability of ligands with the proteins at their active sites through water bridges, hydrophobic interactions, and H-bonding. Our findings suggest Conivaptan and Tegobuvir as potential therapeutic agents against SARS-CoV-2. Further in vitro and in vivo validation and evaluation are warranted to establish how these drug compounds target the Nsp9 replicase and spike proteins.

Source: PubMed

Related molecules

Name	Synonyms	Genes
Conivaptan
nsp9	replicase
Tegobuvir
Phaitanthrin D	3-Oxa-12,20-diazapentacyclo[10.8.0.01,5.06,11.014,19]icosa-6,8,10,14,16,18-hexaene-4,13-dione
Bromocriptine
Baicalin
Spike glycoprotein	Spike protein, S glycoprotein, S-Protein, S1, S2, S3, Peplomer protein, E2	S, ORF2
Telmisartan

Related interactions

Target	Drug	Type	Result
nsp9	Conivaptan	Computational	positive
Spike glycoprotein	Tegobuvir	Computational	positive
nsp9	Telmisartan	Computational	positive
nsp9	Phaitanthrin D	Computational	positive
Spike glycoprotein	Bromocriptine	Computational	positive
Spike glycoprotein	Baicalin	Computational	positive