Identification of naphthyridine and quinoline derivatives as potential Nsp16-Nsp10 inhibitors: a pharmacoinformatics study

被引:28
作者
Aldahham, Bilal J. M. [1 ]
Al-Khafaji, Khattab [2 ]
Saleh, Mohanad Yakdhan [3 ]
Abdelhakem, Adel Mohamed [4 ]
Alanazi, Amer M. [5 ]
Islam, Ataul [6 ,7 ,8 ,9 ]
机构
[1] Univ Anbar, Coll Appl Sci Hit, Dept Chem, Anbar, Hit, Iraq
[2] Gaziantep Univ, Coll Arts & Sci, Dept Chem, Gaziantep, Turkey
[3] Univ Mosul, Coll Educ Pure Sci, Dept Chem, Ninawa, Iraq
[4] Minia Univ, Coll Pharm, Dept Med Chem, Mina, Egypt
[5] King Saud Univ, Coll Pharm, Pharmaceut Chem Dept, Riyadh, Saudi Arabia
[6] Univ Manchester, Div Pharm & Optometry, Sch Hlth Sci, Fac Biol Med & Hlth, Oxford Rd, Manchester M13 9PL, Lancs, England
[7] Univ Kwazulu Natal, Sch Hlth Sci, Durban, South Africa
[8] Univ Pretoria, Fac Hlth Sci, Dept Chem Pathol, Pretoria, South Africa
[9] Tshwane Acad Div, Natl Hlth Lab Serv, Pretoria, South Africa
关键词
Naphthyridine and quinoline derivatives; SARS-CoV-2; Nsp16-Nsp10; COVID-19; virtual screening; molecular dynamics simulation;
D O I
10.1080/07391102.2020.1851305
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
This research is a recent effort to explore some new heterocyclic compounds as novel and potential nonstructural protein-16-nonstructural protein-10 (Nsp16-Nsp10) inhibitors for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) inhibition. The SARS-CoV-2 is causative agent of coronavirus disease 2019 (COVID-19) pandemic. A set of 58 molecules belongs to the naphthyridine and quinoline derivatives have been recently synthesized and considered for structure-based virtual screening against Nsp16-Nsp10. Molecular docking was virtually performed to screen for anti-SARS-CoV-2 activity against Nsp16-Nsp10. Fourteen out of fifty-eight compounds were exhibited binding affinity higher than co-crystal bound ligand s-adenosylmethionine (SAM) toward Nsp16-Nsp10. Further, the in silico pharmacokinetics assessment was carried out and it was found that two molecules possess the acceptable pharmacokinetic profile, hence considered promising Nsp16-Nsp10 inhibitors. The binding interaction analysis was revealed some crucial binding interactions between the final selected two molecules and ligand-binding amino acid residues of Nsp16-Nsp10 protein. In order to explore the characteristics of the protein-ligand complex and how selected small molecules retained inside the receptor cavity in dynamic states, all-atoms conventional molecular dynamics (MD) simulation was performed. Several factors were obtained from the MD simulation trajectory evidently suggested the potentiality of the molecules and stability of the protein-ligand complex. Finally, the binding affinity of both molecules and SAM was explored through the MM-GBSA approach which explained that both molecules possess strong affection towards the Nsp16-Nsp10. Hence, from the pharmacoinformatics assessment, it can be concluded that both heterocyclic compounds might be crucial for SARS-CoV-2 inhibition, subjected to experimental validation. Communicated by Ramaswamy H. Sarma
引用
收藏
页码:3899 / 3906
页数:8
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