Modelling of Hepatitis E virus RNA-dependent RNA polymerase genotype 3 from a chronic patient andin silicointeraction analysis by molecular docking with Ribavirin

自动停靠 利巴韦林 生物信息学 对接(动物) 病毒学 RNA依赖性RNA聚合酶 丙型肝炎病毒 戊型肝炎病毒 计算生物学 生物 基因型 聚合酶 化学 医学 病毒 生物化学 基因 护理部
作者
Florencia Cancela,Santiago Rendón-Marín,Carolina Quintero-Gil,Douglas R. Houston,Gediminas Gumbis,Yanina Panzera,Ruben Pérez,Juan Arbiza,Santiago Mirazo
出处
期刊:Journal of Biomolecular Structure & Dynamics [Taylor & Francis]
卷期号:41 (2): 705-721 被引量:3
标识
DOI:10.1080/07391102.2021.2011416
摘要

Hepatitis E Virus (HEV) infection is an emergent zoonotic disease, where chronic hepatitis E associated to solid organ transplant (SOT) recipients, related to genotype 3, is the clinical manifestation of major concern. In this setting, ribavirin (RBV) treatment is the only available therapy, though drug-resistant variants could emerge leading to a therapeutic failure. Crystallographic structures have not been reported for most of the HEV proteins, including the RNA-polymerase (RdRp). Therefore, the mechanism of action of RBV against HEV and the molecular interactions between this drug and RdRp are largely unknown. In this work, we aimed to model in silico the 3 D structure of a novel HEV3 RdRp (HEV_C1_Uy) from a chronically HEV infected-SOT recipient treated with RBV and to perform a molecular docking simulation between RBV triphosphate (RBVT), 7-methyl-guanosine-5'-triphosphate and the modelled protein. The models were generated using I-TASSER server and validated with multiple bioinformatics tools. The docking analysis were carried out with AutoDock Vina and LeDock software. We obtained a suitable model for HEV_C1_Uy (C-Score=-1.33, RMSD = 10.4 ± 4.6 Å). RBVT displayed a binding affinity of −7.6 ± 0.2 Kcal/mol by molecular docking, mediated by 6 hydrogen-bonds (Q195-O14, S198-O11, E257-O13, S260-O2, O3, S311-O11) between the finger's-palm-domains and a free binding energy of 31.26 ± 16.81 kcal/mol by molecular dynamics simulations. We identified the possible HEV RdRp interacting region for incoming nucleotides or analogs and provide novel insights that will contribute to better understand the molecular interactions of RBV and the enzyme and the mechanism of action of this antiviral drug.Communicated by Ramaswamy H. Sarma.

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
华仔应助科多兽骑士采纳,获得30
刚刚
刚刚
赘婿应助tuyoyo采纳,获得10
1秒前
啦啦啦完成签到,获得积分10
1秒前
GS11完成签到,获得积分10
1秒前
Lucas应助麒麟采纳,获得20
2秒前
温暖冬日完成签到,获得积分10
2秒前
EED发布了新的文献求助10
2秒前
葡萄发布了新的文献求助30
3秒前
小骁同学完成签到,获得积分10
3秒前
朏朏完成签到,获得积分10
4秒前
5km完成签到,获得积分10
5秒前
wanci应助爱学习的曼卉采纳,获得10
5秒前
5秒前
7秒前
8秒前
Theprisoners应助吗喽采纳,获得20
8秒前
王冠军完成签到,获得积分10
8秒前
9秒前
9秒前
认真跳跳糖完成签到,获得积分10
10秒前
Zhao Jiaxu完成签到,获得积分10
10秒前
英俊的铭应助mengxia采纳,获得10
11秒前
在水一方应助abletoo采纳,获得20
12秒前
12秒前
12秒前
明理十三发布了新的文献求助10
13秒前
relink完成签到,获得积分10
14秒前
充电宝应助迷你的颖采纳,获得10
15秒前
16秒前
16秒前
niania发布了新的文献求助10
17秒前
Anxinxin完成签到,获得积分10
18秒前
ding应助ZengJuan采纳,获得10
19秒前
19秒前
20秒前
邓思琪完成签到,获得积分10
20秒前
欣慰碧琴完成签到,获得积分10
20秒前
Maisie发布了新的文献求助10
20秒前
ding应助YZzzJ采纳,获得10
21秒前
高分求助中
A new approach to the extrapolation of accelerated life test data 1000
Indomethacinのヒトにおける経皮吸収 400
基于可调谐半导体激光吸收光谱技术泄漏气体检测系统的研究 370
Phylogenetic study of the order Polydesmida (Myriapoda: Diplopoda) 370
Robot-supported joining of reinforcement textiles with one-sided sewing heads 320
Aktuelle Entwicklungen in der linguistischen Forschung 300
Current Perspectives on Generative SLA - Processing, Influence, and Interfaces 300
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 3992562
求助须知:如何正确求助?哪些是违规求助? 3533545
关于积分的说明 11262757
捐赠科研通 3273163
什么是DOI,文献DOI怎么找? 1805959
邀请新用户注册赠送积分活动 882889
科研通“疑难数据库(出版商)”最低求助积分说明 809513