Mukhtar Mamuna, Khan Haris Ahmed, Ibisanmi Tope Abraham, Faleti Ayodele Ifeoluwa, Zaidi Najam Us Sahar Sadaf
Department of Industrial Biotechnology, Atta ur Rahman School of Applied Biosciences, National University of Sciences and Technology, Islamabad, Pakistan.
Department of Biotechnology, University of Mianwali, Mianwali, Pakistan.
Bioinform Biol Insights. 2024 Jul 27;18:11779322241264144. doi: 10.1177/11779322241264144. eCollection 2024.
Viral infections and associated illnesses account for approximately 3.5 million global fatalities and public health problems. Medicinal plants, with their wide therapeutic range and minimal side effects, have gained limelight particularly in response to growing concerns about drug resistance and sluggish development of antiviral drugs. This study computationally assessed 11 chemical compounds from along with two antiviral drugs to inhibit SARS CoV 2 (coronavirus disease 2019 [COVID-19]) RNA-dependent RNA polymerase (RdRP), influenza virus RdRP, and two crucial dengue virus (DENV) enzymes (NS2B/NS3 protease and NS5 polymerase). Berberine and oxyberberine passed all pharmacokinetics analysis filters including Lipinski rule, blood-brain barrier permeant, and cytochrome suppression and demonstrated drug-likeness, bioavailability, and a non-toxic profile. Docking of phytochemicals from returned promising results with selected viral proteins, ie, DENV NS2BNS3 (punjabine -10.9 kcal/mol), DENV NS5 (punjabine -10.4 kcal/mol), COVID-19 RdRP (oxyacanthine -9.5 kcal/mol), and influenza RdRP (punjabine -10.4 kcal/mol). The optimal pharmacokinetics of berberine exhibited good binding energies with NS2BNS3 (-8.0 kcal/mol), NS5 (-8.3 kcal/mol), COVID RdRP (-7.7 kcal/mol), and influenza RdRP (-8.3 kcal/mol), while molecular dynamics simulation of a 50-ns time scale by GROMACS software package provided insights into the flexibility and stability of the complexes. A hidden treasure trove for antiviral research, berberine, berbamine, berbamunine, oxyberberine, oxyacanthine, baluchistanamine, and sindamine has showed encouraging findings as possible lead compounds. Pharmacological analyses provide credence for the proposed study; nevertheless, as the antiviral mechanisms of action of these phytochemicals are not well understood, additional research and clinical trials are required to demonstrate both their efficacy and toxicity through in vitro and in vivo studies.
病毒感染及相关疾病导致全球约350万人死亡，并引发公共卫生问题。药用植物具有广泛的治疗范围和最小的副作用，尤其在应对人们对耐药性和抗病毒药物研发缓慢日益增长的担忧方面受到关注。本研究通过计算评估了来自[具体来源未提及]的11种化合物以及两种抗病毒药物对严重急性呼吸综合征冠状病毒2（SARS-CoV-2，即2019冠状病毒病[COVID-19]）的RNA依赖性RNA聚合酶（RdRP）、流感病毒RdRP以及两种关键的登革病毒（DENV）酶（NS2B/NS3蛋白酶和NS5聚合酶）的抑制作用。小檗碱和氧化小檗碱通过了所有药代动力学分析筛选，包括Lipinski规则、血脑屏障通透性和细胞色素抑制，并表现出药物相似性、生物利用度和无毒特性。来自[具体来源未提及]的植物化学物质与选定的病毒蛋白对接取得了有前景的结果，即登革病毒NS2B/NS3（刺檗碱 -10.9千卡/摩尔）、登革病毒NS5（刺檗碱 -10.4千卡/摩尔）、COVID-19 RdRP（刺叶番荔枝碱 -9.5千卡/摩尔）和流感RdRP（刺檗碱 -10.4千卡/摩尔）。小檗碱的最佳药代动力学表现出与NS2B/NS3（-8.0千卡/摩尔）、NS5（-8.3千卡/摩尔）、COVID RdRP（-7.7千卡/摩尔）和流感RdRP（-8.3千卡/摩尔）的良好结合能，而由GROMACS软件包进行的50纳秒时间尺度的分子动力学模拟提供了对复合物灵活性和稳定性的见解。小檗碱、小檗胺、巴穆宁碱、氧化小檗碱、刺叶番荔枝碱、俾路支胺和信德胺作为抗病毒研究的潜在宝库，已显示出作为可能的先导化合物的令人鼓舞的发现。药理学分析为该研究所提内容提供了可信度；然而，由于这些植物化学物质的抗病毒作用机制尚未完全了解，需要通过体外和体内研究进行更多研究和临床试验，以证明它们的疗效和毒性。
