Discovery of a Potent Inhibitor to Overcome Carbapenem Resistance in Pseudomonas aeruginosa Strains via Inhibition of VIM-2 Metallo-β-lactamases

Author:

Moosavi Seyedeh SaraORCID,Madani MahboobehORCID,Mirzaie SakoORCID,Hosseini Jazani NimaORCID

Abstract

Background: Mutations in bacteria frequently occur that display a crucial need for new antimicrobial agents. Metallo-β-lactamases (MBLs) are a growing threat to maintaining the effectiveness of beta-lactam antibiotics. Resistance to beta-lactam antibiotics is one of the most common types of antibiotic resistance, which causes the ineffectiveness of antibiotics. Objectives: This study aimed to identify a novel inhibitor using molecular dynamics simulations to inhibit VIM-2 Metallo-β-lactamases and overcome carbapenem resistance in Pseudomonas aeruginosa strains. Methods: Computational biology tools were employed for this study, including molecular dynamics, binding free energy, virtual screening, and docking. Natural compounds were taken from the ZINC databank and prepared. At the next stage, the prepared compounds were screened based on docking energy in the active site of VIM-2 MBL by Schrödinger (Maestro) software, and better compounds were selected. Captopril was chosen as a positive control inhibitor for VIM-2 MBLs. Ultimately, molecular dynamics simulations were performed using GROMACS software, and outputs were analyzed. Results: Maestro software's screening results showed that ZINC00517765 was the best inhibitor with -12.29 kcal mol-1 docking energy. The ADME investigations revealed that ZINC00517765 had an appropriate range of pharmacokinetics, lipophilicity, and drug-likeness features as an inhibitor of VIM-2 MBL. Molecular dynamics outcomes explicated that VIM-2 MBL in the presence of ZINC00517765 had better stability during simulation. The results of the MM-PBSA study illustrated that ZINC00517765 with -72.29 kJ mol-1 binding free energy was more potent than Captopril with -23.39 kJ mol-1. Conclusions: This study showed that VIM-2 MBL in the presence of ZINC00517765 has suitable stability during simulation. Also, more hydrogen bonds and stronger binding free energy than Captopril confirm that ZINC00517765 is a proper candidate for further studies and laboratory investigation.

Publisher

Briefland

Cited by 1 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3