论文标题
混合方法以鉴定针对COVID-19 3Cl蛋白酶的药物液化性铅化合物
Hybrid Approach to Identify Druglikeness Leading Compounds against COVID-19 3CL Protease
论文作者
论文摘要
SARS-COV-2是一种积极的单链RNA基本分子，自2022年6月以来，已导致超过630万人死亡。此外，由于通过锁定扰乱了全球供应链，该病毒对全球经济造成了巨大的破坏。设计和开发该病毒及其各种变体的药物至关重要。在本文中，我们开发了一种基于研究的研究杂种框架，以重新利用现有的治疗剂，以发现可以治疗Covid-19的药物样生物活性分子。我们对从Chembl数据库检索的分子进行了Lipinski规则，并发现针对SARS冠状病毒3Cl蛋白酶的133种药物生物活性分子。基于标准IC50，数据集分为三类，活动性，无效和中间体。我们的比较分析表明，与梯度提升，XGBoost，支持载体，决策树和基于森林的回归器模型相比，提出的基于QSAR的额外树回收期（ETR）模型改善了与化合物的生物活性相关的预测结果。进行ANDET分析以确定具有Chembl ID的13个生物活性分子187460，190743，222234，222628，222735，222735，222769，222840，222893，222893，225515，225515，358279，358279，363535，3635135，365134和42634和426898.898。 SARS-COV-2 3Cl蛋白酶。在下一步中，使用分子对接的结合亲和力计算生物活性分子的功效，然后将六个使用Chembl IDS 187460、222769、2255515、358279、358279、363535和3655134的生物活性分子入围了六个生物活性分子。预计药物学家/药物制造商将进一步研究这六个分子，以寻找适合SARS-COV-2的药物候选物。他们可以为下游药物开发阶段采用这些有希望的化合物。
SARS-COV-2 is a positive single-strand RNA-based macromolecule that has caused the death of more than 6.3 million people since June 2022. Moreover, by disturbing global supply chains through lockdown, the virus has indirectly caused devastating damage to the global economy. It is vital to design and develop drugs for this virus and its various variants. In this paper, we developed an in-silico study-based hybrid framework to repurpose existing therapeutic agents in finding drug-like bioactive molecules that would cure Covid-19. We employed the Lipinski rules on the retrieved molecules from the ChEMBL database and found 133 drug-likeness bioactive molecules against SARS coronavirus 3CL Protease. Based on standard IC50, the dataset was divided into three classes active, inactive, and intermediate. Our comparative analysis demonstrated that the proposed Extra Tree Regressor (ETR) based QSAR model has improved prediction results related to the bioactivity of chemical compounds as compared to Gradient Boosting, XGBoost, Support Vector, Decision Tree, and Random Forest based regressor models. ADMET analysis is carried out to identify thirteen bioactive molecules with ChEMBL IDs 187460, 190743, 222234, 222628, 222735, 222769, 222840, 222893, 225515, 358279, 363535, 365134 and 426898. These molecules are highly suitable drug candidates for SARS-COV-2 3CL Protease. In the next step, the efficacy of bioactive molecules is computed in terms of binding affinity using molecular docking and then shortlisted six bioactive molecules with ChEMBL IDs 187460, 222769, 225515, 358279, 363535, and 365134. These molecules can be suitable drug candidates for SARS-COV-2. It is anticipated that the pharmacologist/drug manufacturer would further investigate these six molecules to find suitable drug candidates for SARS-COV-2. They can adopt these promising compounds for their downstream drug development stages.
