Abstract
The N terminal domain (NTD) of Nucleocapsid protein (N protein) of coronavirus (CoV) binds to the viral (+) sense RNA and results in CoV ribonucleoprotien (CoV RNP) complex, essential for the virus replication. In this study, the RNA-binding N terminal domain (NTD) of the N protein was targeted for the identification of possible inhibitors of RNA binding. Two NTD structures of N proteins were selected (2OFZ and 1SSK, 92% homology) for virtual screening of 56,079 compounds from Asinex and Maybridge library to identify top 15 hits for each of the targets based on ‘docking score’. These top-hits were further screened for MM-GBSA binding free energy, pharmacokinetic properties (QikProp) and drug-likeness (SwissADME) and subjected to molecular dynamics (MD) studies. Two suitable binders (ZINC00003118440 and ZINC0000146942) against the target 2OFZ were identified. ZINC00003118440 is a theophylline derivative under the drug class ‘bronchodilators’ and further screening with approved bronchodilators was also studied to identify their ability to bind to the RNA binding region on the N protein. The other identified top hit is ZINC0000146942, which is a 3,4dihydropyrimidone class molecule. Hence this study suggests two important class of compounds, theophylline and pyrimidone derivaties as possible inhibitors of RNA binding to the N terminal domain of N protein of coronavirus, thus opening new avenues for in vitro validations. Communicated by Ramaswamy H. Sarma.
Keywords: 2019 novel corona virus; 2019-nCoV; N terminal domain; Nucleocapsid protein; RNA binding; SARS-CoV-2; drug design.
【저자키워드】 SARS-CoV-2, drug design, 2019-nCoV, nucleocapsid protein, RNA binding, 2019 novel corona virus, N terminal domain, 【초록키워드】 Structure, coronavirus, drug design, Virtual screening, molecular dynamics, in vitro, binding free energy, inhibitors, drug-likeness, nucleocapsid protein, free energy, RNA, Protein, N protein, CoV, virus replication, target, NTD, targets, molecular, inhibitor, novel corona virus, binding, compounds, pharmacokinetic, N terminal domain, theophylline, complex, Compound, nCoV, homology, docking score, N proteins, N Terminal, pyrimidone, bind, selected, identify, approved, screened, the N protein, 【제목키워드】 RNA, inhibitor, binding, N-protein,