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Qualitative and quantitative phytochemical composition and antimicrobial activity of different solvent extracts of Hardwickia binata Roxb. Hardwickia binata Roxb 不同溶剂提取物的定性和定量植物化学成分及抗菌活性。
IF 0.2 Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-01-31 DOI: 10.25303/1903rjbt031038
Manimegalai Peraman, Selvam Kuppusamy
Hexane and ethyl acetate extracts were employed to carry out the research on the phytochemical and antibacterial activity of Hardwickia binata Roxb. To identify the components, present in the extract, the GC-MS technique was used for analysis. Functional groups of various extracts were identified using FTIR. The plant extract in hexane and ethyl acetate was evaluated for its ability to fight human pathogenic bacteria. The results of the phytochemical screening revealed that phenols, saponins, flavonoids, cardiac glycosides, steroids and tannins are present. The GC-MS data revealed that the ethyl acetate extract contained 25 bioactive substances. The extract of ethyl acetate showed good antimicrobial activity. S. aureus (16 mm) demonstrated the largest zone of inhibition when treated with 75 μg/mL of ethyl acetate extracts. As a result, this study provides data on the phytochemical constituents identified in both extracts. As a result, it may be employed in additional therapeutic applications in near future.
研究人员采用正己烷和乙酸乙酯提取物来研究 Hardwickia binata Roxb 的植物化学成分和抗菌活性。为了确定提取物中的成分,采用了气相色谱-质谱(GC-MS)技术进行分析。使用傅立叶变换红外光谱鉴定了各种提取物的官能团。对正己烷和乙酸乙酯中的植物提取物进行了抗人类致病菌能力的评估。植物化学筛选结果表明,其中含有酚类、皂苷、黄酮类、强心苷、类固醇和单宁酸。气相色谱-质谱数据显示,乙酸乙酯提取物中含有 25 种生物活性物质。乙酸乙酯提取物显示出良好的抗菌活性。当使用 75 μg/mL 的乙酸乙酯提取物处理金黄色葡萄球菌(16 毫米)时,其抑制区最大。因此,本研究提供了在两种提取物中发现的植物化学成分的数据。因此,在不久的将来,它可能会被用于更多的治疗用途。
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引用次数: 0
A molecular docking study on inhibition of HMG CoA reductase with respect to phytochemicals of Terminalia cuneata Roth. 关于抑制 HMG CoA 还原酶与 Terminalia cuneata Roth 植物化学物质的分子对接研究。
IF 0.2 Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-01-31 DOI: 10.25303/1903rjbt1080119
Rini Abraham
Inhibition of cholesterol synthesis by targeting the enzyme hydroxyl methyl glutarate coenzyme reductase (HMGCR), a rate-limiting enzyme in the mevalonate pathway, has been identified as a promising approach. The most commonly employed drugs for the treatment of hyperlipidemia, statins, have been identified with some risk factors for muscle-related side effects. In this present study, an attempt is made to inhibit the HMG-CoA reductase enzyme using phytochemicals of Terminalia cuneata by in silico approach. The software AutoDock 4.2 was used for the docking study. We used atorvastatin and lovastatin as positive control. We also found the drug likeliness and bioactivity score of all inhibitors using the mol-inspiration prediction tool. We found that most of the compounds showed the best binding energy results against the targeted enzyme.
通过靶向甲羟戊酸途径中的限速酶羟基甲基戊二酸辅酶还原酶(HMGCR)来抑制胆固醇的合成,已被认为是一种很有前景的方法。治疗高脂血症最常用的药物他汀类药物已被确认存在一些导致肌肉相关副作用的风险因素。在本研究中,我们尝试采用硅学方法,利用杉属植物化学物质来抑制 HMG-CoA 还原酶。对接研究使用了 AutoDock 4.2 软件。我们使用阿托伐他汀和洛伐他汀作为阳性对照。我们还利用分子启发预测工具发现了所有抑制剂的药物相似性和生物活性得分。我们发现,大多数化合物都显示出了与目标酶的最佳结合能。
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引用次数: 0
Evaluation of neuroprotective effect and identification of active compounds from Nigella sativa Linn. through bioactive guided fractionation 通过生物活性引导分馏评估神经保护作用并鉴定芝麻中的活性化合物
IF 0.2 Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-01-31 DOI: 10.25303/1903rjbt039047
S. Sudha, B. Chitra, Nisha S. Arif
The medicinal herb Nigella sativa Linn of the Ranunculaceae family is widely used everywhere in the world. In the past, numerous illnesses and disorders have been treated with N. sativa L. seeds. Both in vivo and in vitro analyses revealed that N. sativa L., possesses numerous neuroprotective effects. The methanolic extract of N. sativa L. was evaluated for the presence of antioxidant and anticholinesterase activity and the findings revealed that the extract has outstanding antioxidant and anticholinesterase activity. Since the extract was found to possess excellent activity, the methanolic extract was separated using column chromatography with the aid of bioactive guided fractionation. A total of 19 fractions were collected and analyzed for antioxidant potential. The active fractions were collected, pooled and analyzed using LC-MS techniques. The outcomes revealed the existence of Kaempferol 3-(2-galloyl-alpha-L-arabinopyranoside). To assess the safety aspects of methanolic extract, a subacute toxicity test was performed using zebrafish. The results of the liver function test and histoarchitecture analysis found that there were no adverse consequences from the extract. Altogether, these results suggest that N. sativa L., could be a promising therapeutic drug against Alzheimer’s disease.
兰科药草 Nigella sativa Linn 在世界各地被广泛使用。过去,许多疾病都是用 N. sativa L. 种子治疗的。体内和体外分析表明,N. sativa L. 具有多种神经保护作用。对 N. sativa L. 的甲醇提取物进行了抗氧化和抗胆碱酯酶活性评估,结果表明该提取物具有出色的抗氧化和抗胆碱酯酶活性。由于发现该提取物具有出色的活性,因此借助生物活性引导分馏技术,使用柱层析法对甲醇提取物进行了分离。总共收集了 19 个馏分,并对其抗氧化潜力进行了分析。对活性馏分进行收集、汇集,并使用 LC-MS 技术进行分析。结果显示存在堪非醇 3-(2-galloyl-alpha-L-阿拉伯吡喃糖苷)。为了评估甲醇提取物的安全性,使用斑马鱼进行了亚急性毒性试验。肝功能测试和组织结构分析的结果表明,甲醇提取物没有产生不良后果。总之,这些结果表明,N. sativa L. 是一种很有前景的治疗阿尔茨海默病的药物。
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引用次数: 0
Time series forecasting cancers cases in Algeria using double exponential smoothing method 使用双指数平滑法对阿尔及利亚癌症病例进行时间序列预测
IF 0.2 Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2024-01-31 DOI: 10.25303/1903rjbt01012
Talbi Melissa, Adjebli Ahmed, Tighilet Karim, Louardiane Mustapha, Messis Abdelaziz
Cancers are the second cause of death worldwide. Prevalence and incidence of cancers are getting increased by aging and population growth. This study aims to predict and model the evolution of breast, colorectal, lung, bladder and prostate cancers over the period of 2014-2019. In this study, data were analyzed using time series analysis with double exponential smoothing method to forecast the future pattern. To describe and fit the appropriate models, Minitab statistical software version 17 was used. Between 2014 and 2019, the overall trend in the raw number of new cancer cases registered has been increasing over time; the change in observations over time has been increasing. Our forecast model is validated since we have good prediction for the period 2020 and data are not available for 2021 and 2022. Time series analysis showed that the double exponential smoothing is an efficient tool to model the future data on the raw number of new cancer cases.
癌症是全球第二大死因。随着老龄化和人口增长,癌症的流行率和发病率不断上升。本研究旨在预测 2014-2019 年期间乳腺癌、结直肠癌、肺癌、膀胱癌和前列腺癌的演变情况并建立模型。本研究采用时间序列分析和双指数平滑法分析数据,以预测未来模式。为了描述和拟合适当的模型,使用了 Minitab 统计软件版本 17。从 2014 年到 2019 年,新登记癌症病例的原始数量总体呈逐年上升趋势;观测值随时间的变化也在不断增加。由于我们对 2020 年的预测结果良好,而 2021 年和 2022 年的数据尚未获得,因此我们的预测模型得到了验证。时间序列分析表明,双指数平滑法是建立未来癌症新病例原始数据模型的有效工具。
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引用次数: 0
In silico molecular docking studies of 2, 4 and 2, 6-di-tert-butylphenol against NAGK and SPP1 proteins to recuperate rheumatoid arthritis 2、4 和 2、6-二叔丁基苯酚与 NAGK 和 SPP1 蛋白的分子对接研究,以治疗类风湿性关节炎
IF 0.2 Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-11-05 DOI: 10.25303/1812rjbt043047
S. Singh, T. Qidwai
Rheumatoid arthritis (RA) is a chronic autoimmune disorder that primarily affects the synovial joints. It is connected to progressive disability, early death and socioeconomic burdens. So, there is an urgent need to develop novel drugs that effectively treat patients at each stage of disease progression. N-acetylglucosamine kinase (NAGK) and secreted phosphoprotein 1(SPP1) are two attractive drug targets for RA. NAGK protein converts endogenous N-acetyl-D-glucosamine (GlcNAc) into GlcNAc 6-phosphate. GlcNAc has suppressive effects on experimental RA in mouse models. SPP1 stimulates the synthesis of a key proinflammatory cytokine implicated in the pathogenesis of RA. In order to design new drug candidates, crystal structure of human NAGK (PDB Id: 2CH5) was retrieved from the protein data bank. Amino acid sequence of SPP1 (Uniprot Id: P10451) was retrieved from uniprot database and modeled by the Phyre2 server. Computed SPP1 model energy was minimized using the YASARA energy minimization server and validated by the Ramachandran plot and the ProSA-web error-detection tool. 2, 4-Di-tert-butylphenol and 2, 6-Di-Tert-butylphenol are known compound isolates from bark extract of Schleichera oleosa having anti-arthritic and anti-inflammatory activities as accessed by PASS online server. These compounds were docked against active site of NAGK and SPP1 proteins using MTiAutoDock server. The binding affinity of these compounds against NAGK and SPP1 proteins ranges from -6.12 to -7.17 kcal/mol. The findings of this study will open the way for the development of herbal remedies for rheumatoid arthritis based on the Schleichera oleosa plant, potentially leading to the development of novel drugs.
类风湿性关节炎(RA)是一种主要影响滑膜关节的慢性自身免疫性疾病。它与渐进性残疾、早死和社会经济负担有关。因此,迫切需要开发新型药物,在疾病进展的各个阶段对患者进行有效治疗。N-乙酰葡糖胺激酶(NAGK)和分泌型磷蛋白1(SPP1)是治疗RA的两个具有吸引力的药物靶点。NAGK 蛋白可将内源性 N-乙酰-D-葡糖胺(GlcNAc)转化为 GlcNAc 6-磷酸。GlcNAc 对小鼠模型中的实验性 RA 有抑制作用。SPP1 可刺激一种关键的促炎细胞因子的合成,这种细胞因子与 RA 的发病机制有关。为了设计新的候选药物,我们从蛋白质数据库中检索到了人类 NAGK(PDB Id:2CH5)的晶体结构。从uniprot数据库中检索了SPP1(Uniprot Id:P10451)的氨基酸序列,并通过Phyre2服务器建立了模型。利用 YASARA 能量最小化服务器将计算出的 SPP1 模型能量最小化,并通过拉马钱德兰图和 ProSA-web 错误检测工具进行验证。2,4-二叔丁基苯酚和2,6-二叔丁基苯酚是从Schleichera oleosa树皮提取物中分离出来的已知化合物,具有抗关节炎和消炎活性。这些化合物通过 MTiAutoDock 服务器与 NAGK 和 SPP1 蛋白的活性位点对接。这些化合物与 NAGK 和 SPP1 蛋白的结合亲和力为 -6.12 至 -7.17 kcal/mol。这项研究的发现将为开发基于油茶属植物的类风湿关节炎草药疗法开辟道路,并有可能开发出新型药物。
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引用次数: 0
Free amino acid profiling and quantification of 4-hydroxyisoleucine in Trigonella foenum-graecum (fenugreek) seeds treated with Trichoderma viride and rhizobium 用病毒毛霉和根瘤菌处理的葫芦巴种子中的游离氨基酸谱分析和 4-羟基异亮氨酸的定量分析
IF 0.2 Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-11-05 DOI: 10.25303/1812rjbt014042
Haritha Addala, Lalitha Pappu
Fenugreek is a legume but regarded as a poor nitrogen fixer. The present study deals with the marked effect of Trichoderma viride and rhizobium on quantification of 4-hydroxyisoleucine content and free amino acid composition of fenugreek seeds. 4-hydroxyisoleucine is regarded as an antidiabetic compound present specifically in fenugreek plants. Fenugreek seeds treated with both T.viride and rhizobium boosted free amino acid concentration and 4-hydroxyisoleucine content compared to control and positive control (NPK treated). Seeds were treated with T.viride suspension (107 spores/seed), rhizobium suspension (108 cells/seed) , combination of T.viride and rhizobium suspension in equal amounts (0.5ml of T.viride  0.5ml of rhizobium suspension /seed), NPK suspension ( 1ml NPK suspension / seed) and untreated seeds (1 ml distilled water/ seed) serving as control sown in pots filled with potting soil and also in a randomized plot ( 55 feet) in the field. In free amino acid composition, isoleucine is the precursor for 4-hydroxyisoleucine compound and its concentration was enhanced by 47.79 % (potted plants) and 26.46 % (field plants) over control and by 27.02 % (potted plants) and 13.03 % (field plants) over positive control. 4-hydroxyisoleucine content was quantified using LCMS method in both potted and field plants. An increase of 37.02 % (potted plants) and 23.61 % (field plants) in 4-hydroxyisoleucine concentration in dual treated plants over control and positive control was observed.
胡芦巴是一种豆科植物,但被认为固氮能力差。本研究探讨了毛霉菌和根瘤菌对葫芦巴种子中 4-羟基异亮氨酸含量和游离氨基酸组成定量的显著影响。4- 羟基异亮氨酸被认为是葫芦巴植物中特有的一种抗糖尿病化合物。与对照组和阳性对照组(氮磷钾处理)相比,用T.viride和根瘤菌处理的葫芦巴种子提高了游离氨基酸浓度和4-羟基异亮氨酸含量。种子经病毒唑悬浮液(107 个孢子/种子)、根瘤菌悬浮液(108 个细胞/种子)、病毒唑和根瘤菌等量混合悬浮液(0.5 毫升病毒唑悬浮液  0.5 毫升根瘤菌悬浮液/种子)、氮磷钾悬浮液(1 毫升氮磷钾悬浮液/种子)和未经处理的种子(1 毫升蒸馏水/种子)处理后作为对照,播种在装满盆土的花盆中,也播种在田间的随机小区(55 英尺)中。在游离氨基酸组成中,异亮氨酸是 4-羟基异亮氨酸化合物的前体,其浓度比对照提高了 47.79 %(盆栽植物)和 26.46 %(大田植物),比阳性对照提高了 27.02 %(盆栽植物)和 13.03 %(大田植物)。采用 LCMS 方法对盆栽植物和大田植物中的 4-羟基异亮氨酸含量进行了定量。与对照和阳性对照相比,经双重处理的植物中 4-羟基异亮氨酸的浓度分别增加了 37.02 %(盆栽植物)和 23.61 %(大田植物)。
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引用次数: 0
Facile Preparation and Characterization of Alginate and Triton X-100 Zinc Phosphate modified Surface Nanocrystals as a Novel Anti-corrosive and Antibacterial agent 藻酸盐和 Triton X-100 磷酸锌修饰表面纳米晶体作为新型抗腐蚀和抗菌剂的简便制备与表征
IF 0.2 Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-11-05 DOI: 10.25303/1812rjbt910101
Arezoo Mohammadkhani, Sadjadi Mirabdullah Seyed, N. Farhadyar, F. Mohammadkhani
In this study, two surface-modified antibacterial and anti-corrosive nanoparticles (ZnP-T, ZnP-ALG) were synthesized by facile and efficient one-step ultrasonic synthesis method. Nanocrystals were characterized by X-ray Diffraction (XRD), Fourier Transform Infrared (FT-IR), Energy Dispersive X-Ray Analysis (EDX), Scanning Electron Microscopy (SEM) and Transmission electron microscopy (TEM). The TEM image showed that the product had good dispersion with a particle size of 10-23, 15–32 nm respectively. Antibacterial and cytocompatibility properties were studied by agar diffusion, in vitro viability and cytotoxicity assay (MTT) and colony-forming-unit (CFU). Antibacterial rate of the ZnP-T and ZnP-ALG nanoparticles reached near 100% and cell viability was near 100%. The corrosion resistance of ZnP-T and ZnP-ALG was evaluated by the electrochemical impedance spectroscopy (EIS) approach. Nyquist diagrams demonstrated that the ZnP-ALG sample had better protection than the ZnP-T sample at all immersion time . The frequency phase angle of the ZnP-ALG sample (θ10 kHz) has a greater value compared with the ZnP-T case.
本研究采用简便高效的一步超声合成法合成了两种表面修饰的抗菌防腐纳米粒子(ZnP-T、ZnP-ALG)。通过 X 射线衍射(XRD)、傅立叶变换红外(FT-IR)、能量色散 X 射线分析(EDX)、扫描电子显微镜(SEM)和透射电子显微镜(TEM)对纳米晶体进行了表征。TEM 图像显示,产品具有良好的分散性,粒径分别为 10-23 纳米和 15-32 纳米。抗菌和细胞相容性通过琼脂扩散、体外活力和细胞毒性测定(MTT)以及菌落形成单位(CFU)进行了研究。ZnP-T 和 ZnP-ALG 纳米粒子的抗菌率接近 100%,细胞存活率接近 100%。ZnP-T 和 ZnP-ALG 的抗腐蚀性是通过电化学阻抗光谱(EIS)方法进行评估的。奈奎斯特图显示,在所有浸泡时间内,ZnP-ALG 样品都比 ZnP-T 样品具有更好的保护性能。与 ZnP-T 样品相比,ZnP-ALG 样品的频率相位角(θ10 kHz)值更大。
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引用次数: 0
Calotropis procera leaf extract against paracetamol induced hepatotoxicity in Rats by regulating JNK/ASK-1 Signaling Pathway 石菖蒲叶提取物通过调节 JNK/ASK-1 信号通路对抗扑热息痛诱导的大鼠肝毒性
IF 0.2 Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-11-05 DOI: 10.25303/1812rjbt1220129
K. K. Agrawal, Y. Murti
The goal of the study was to assess the hepatoprotective efficacy of young Calotropis procera leaves. The young leaves of Calotropis procera were extracted by cold maceration with ultra-sonication using chloroform, ethyl acetate and distilled water. Male Wistar rats were used for hepatoprotective evaluation and the body weight, liver weight, serum biomarkers and anti-oxidant markers were measured during study. The extract/fractions significantly (P<0.05) increased the absolute and relative weight of the liver of rats at the dose of 200 mg/kg. It also suppressed the serum biomarkers (P<0.05) in the aforementioned doses. Oral administration of extract/fractions significantly increase the oxidative marker and decreased the progression of paracetamol induced hepatotoxicity. The result of the study suggested that Calotropis procera leaf extract/fractions can reduce hepatotoxicity caused by paracetamol.
这项研究的目的是评估草苁蓉嫩叶的保肝功效。研究人员使用氯仿、乙酸乙酯和蒸馏水,通过冷浸渍和超音波法萃取了草决明嫩叶。研究过程中对雄性 Wistar 大鼠的体重、肝脏重量、血清生物标志物和抗氧化标志物进行了测量。在剂量为 200 毫克/千克时,提取物/馏分能明显增加大鼠肝脏的绝对和相对重量(P<0.05)。在上述剂量下,它还抑制了血清生物标志物(P<0.05)。口服提取物/馏分可明显增加氧化标志物,并降低扑热息痛诱导的肝毒性进展。研究结果表明,石菖蒲叶提取物/萃取物可以减轻扑热息痛引起的肝毒性。
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引用次数: 0
Antioxidant and Antibacterial activity of Lotus tea in Thua Thien Hue province from Vietnam 越南顺化省莲花茶的抗氧化和抗菌活性
IF 0.2 Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-11-05 DOI: 10.25303/1812rjbt048054
N. T. Q. Trang, Ngo Quy Thao Ngoc, Dang Thanh Long, Pham Thanh
In this study, we determined the antioxidant and antibacterial activity in different types of lotus tea (Nelumbo nucifera Gaernt.) in Thua Thien Hue province, Vietnam. The results showed that in four types of lotus tea, the catalase enzyme activity was 0.92-1.35 U/mg protein, the peroxidase enzyme activity was 0.97-2.67 U/mg protein, ascorbic acid content was 0.088-0.135%, the IC50 value was 4.98-6.03 mg/mL and all four kinds of lotus tea inhibited bacteria to a variable extent with low sensitivity. The inhibition zone’s mean diameter increased from 0.23 cm to 0.77 cm. The flower lotus tea gave the highest results on most of the research criteria and the lowest was lotus rhizome tea. From obtained results, tea produced from lotus plants grown in Thua Thien Hue province, Vietnam has a high potential for antioxidant and antibacterial properties.
本研究测定了越南顺化省不同类型荷花茶(Nelumbo nucifera Gaernt.)的抗氧化和抗菌活性。结果表明,在四种荷花茶中,过氧化氢酶活性为 0.92-1.35 U/mg 蛋白,过氧化物酶活性为 0.97-2.67 U/mg 蛋白,抗坏血酸含量为 0.088-0.135% ,IC50 值为 4.98-6.03 mg/mL,四种荷花茶对细菌都有不同程度的抑制作用,敏感性较低。抑菌区的平均直径从 0.23 厘米增至 0.77 厘米。在大多数研究标准中,荷花茶的结果最高,荷叶茶的结果最低。从研究结果来看,越南顺化省种植的莲花茶具有很高的抗氧化和抗菌潜力。
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引用次数: 0
The repurposing of FDA-approved drugs to stop viral replication in COVID-19 treatment: a comprehensive molecular docking and dynamics analysis 在 COVID-19 治疗中重新利用 FDA 批准的药物阻止病毒复制:分子对接和动力学综合分析
IF 0.2 Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-11-05 DOI: 10.25303/1812rjbt055066
Dammalli Manjunath, S.G. Bhavya, Murthy K. R. Shadakshara, S. Rajashekhara, B.E. Rangaswamy
Amidst a public health crisis such as the SARS-CoV-2 induced COVID-19 pandemic, the urgency to develop and provide access to novel drugs becomes paramount. In these scenarios, repurposing existing drugs emerges as an appealing strategy due to their established safety profiles and prior regulatory approvals, potentially streamlining their adoption for new therapeutic purposes. There has been a notable interest in investigating the repurposing potential of FDA-approved drugs to combat the disease triggered by the SARS-CoV-2 virus. This investigation was conducted with the objective of identifying FDA-approved antiviral drugs that could target both the original and mutant forms of the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) protein, given the escalating prevalence of SARS-CoV-2 mutations that undermined vaccine efficacy and underscored the need for alternative treatment avenues. Despite ongoing clinical trials, the selection of drugs specifically designed to combat SARS-CoV-2 remains limited. The present study aimed to assess the inhibitory potential of eight approved antiviral drugs. The wild-type and mutant (P323L) RdRp protein (PDB ID: 7BV2). By utilizing molecular docking techniques, the selected drugs were evaluated based on their binding affinities with both the mutant and wild-type RdRp protein. Subsequently, the protein-ligand complexes exhibiting the highest binding affinities were subjected to a 150 ns molecular dynamics simulation to evaluate their stability. The outcomes of the molecular docking analysis pinpointed Dolutegravir and Beclabuvir as possessing the most robust binding affinities for both mutant and wild-type RdRp systems. These findings prompted the selection of these drugs for an in-depth molecular dynamic simulation (MDS) investigation. The comprehensive analysis of Root Mean Square Deviation (RMSD), Root Mean Square Fluctuation (RMSF), Radius of Gyration (Rg), Solvent Accessible Surface Area (SASA) and Secondary Structure Dynamics confirmed that Dolutegravir and Beclabuvir are potent inhibitors of the NSP12 protein. Collectively, the computational assessments put forth two potential contenders: Dolutegravir and Beclabuvir as promising inhibitors against both the wild-type and mutant RdRp proteins. To further validate these drug candidates, rigorous in vitro and in vivo investigations are warranted which could eventually position them as valuable therapeutic agents in the fight against COVID-19.
在 SARS-CoV-2 引发的 COVID-19 大流行等公共卫生危机中,开发和提供新型药物的紧迫性变得至关重要。在这种情况下,重新利用现有药物成为一种有吸引力的策略,因为这些药物具有公认的安全性,并已获得监管部门的批准,有可能简化将其用于新治疗目的的程序。人们对研究美国食品及药物管理局(FDA)批准的药物在抗击 SARS-CoV-2 病毒引发的疾病方面的再利用潜力产生了显著的兴趣。鉴于 SARS-CoV-2 基因突变的发生率不断上升,削弱了疫苗的疗效,并突出了对替代治疗途径的需求,这项调查的目的是确定 FDA 批准的抗病毒药物,这些药物可以针对 SARS-CoV-2 RNA 依赖性 RNA 聚合酶(RdRp)蛋白的原始形式和突变形式。尽管目前正在进行临床试验,但专门用于抗击 SARS-CoV-2 的药物选择仍然有限。本研究旨在评估八种已获批准的抗病毒药物的抑制潜力。野生型和突变型(P323L)RdRp 蛋白(PDB ID:7BV2)。利用分子对接技术,根据药物与突变型和野生型 RdRp 蛋白的结合亲和力对所选药物进行了评估。随后,对表现出最高结合亲和力的蛋白质配体复合物进行了 150 ns 的分子动力学模拟,以评估其稳定性。分子对接分析的结果表明,Dolutegravir 和 Beclabuvir 与突变型和野生型 RdRp 系统的结合亲和力最强。这些发现促使我们选择这两种药物进行深入的分子动态模拟(MDS)研究。对均方根偏差(RMSD)、均方根波动(RMSF)、回旋半径(Rg)、溶剂可及表面积(SASA)和二级结构动力学的综合分析证实,多鲁特韦和贝拉布韦是 NSP12 蛋白的强效抑制剂。总之,计算评估提出了两个潜在的竞争者:Dolutegravir和Beclabuvir有望成为野生型和突变型RdRp蛋白的抑制剂。为了进一步验证这些候选药物,有必要进行严格的体外和体内研究,最终使它们成为抗击 COVID-19 的重要治疗药物。
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引用次数: 0
期刊
Research Journal of Biotechnology
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