Barkat Md Abul, Fatima Afreen, Riaz Bushra, Hassan Mohd Zaheen, Ahamad Tanveer, Alanezi Abdulkareem A, Barkat Harshita, Almuqati Afaf F, Asiri Yahya I, Siddiqui Sahabjada
Department of Pharmaceutics, College of Pharmacy, University of Hafr Al-Batin, Al Jamiah, 39524, Hafr Al Batin, Saudi Arabia.
Department of Pharmacy Practice, College of Pharmacy, University of Hafr Al Batin, 39524, Hafr Al Batin, Saudi Arabia.
BMC Complement Med Ther. 2025 Jan 30;25(1):32. doi: 10.1186/s12906-024-04738-1.
The spreading of COVID-19 has posed a risk to global health, especially for lung cancer patients. An investigation is needed to overcome the challenges of COVID-19 pathophysiology and lung cancer disease. This study was designed to evaluate the phytoconstituents in Punica granatum peel (PGP), its anti-lung cancer activity, and in silico evaluation for antiviral potential. GC-MS technique was used to detect the phytoconstituents. Cytotoxicity was analyzed using MTT dye, followed by apoptosis, ROS generation, and cell cycle phase detection in human lung cancer cells (A549). The glide module of Maestro software was used to investigate the molecular-docking interaction of the constituents against main protease (Mpro) and papain-like protease (PLpro) of SARS-CoV-2. GROMACS 2023.2 was utilized to evaluate the complex stability. A total of nineteen phytocomponents were detected in the PGP extract through GC-MS analysis. PGP has shown a potential to reduce lung cancer cell proliferation while evading normal cell death. PGP induced apoptosis by arresting cells in the G0/G1 phase and generating ROS. A total of six and eight phytocomponents had a high affinity for PLpro and Mpro proteins, respectively. The top docked complex, ethyl 5-oxo-2-pyrrolidinecarboxylate, with PLpro and Mpro proteins, showed likely stable interaction throughout 100 ns simulation. This finding raises the possibility of top-eight hits (docking score ≥ -1.0 kcal/mol) preventing SARS-CoV-2 severity. The phytoconstituents exhibited orally active drugs with no more than one violation and drug-likeness activity. The PGP phytoconstituents are suggested to be dual agents for lung cancer and SARS-CoV-2 pathogenesis.
新型冠状病毒肺炎（COVID-19）的传播对全球健康构成了威胁，尤其是对肺癌患者。需要进行一项调查，以克服COVID-19病理生理学和肺癌疾病带来的挑战。本研究旨在评估石榴皮（PGP）中的植物成分、其抗肺癌活性以及对抗病毒潜力的计算机模拟评估。采用气相色谱-质谱联用（GC-MS）技术检测植物成分。使用MTT染料分析细胞毒性，随后在人肺癌细胞（A549）中检测凋亡、活性氧（ROS）生成和细胞周期阶段。利用Maestro软件的Glide模块研究这些成分与严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的主要蛋白酶（Mpro）和类木瓜蛋白酶（PLpro）的分子对接相互作用。使用GROMACS 2023.2评估复合物稳定性。通过GC-MS分析在PGP提取物中总共检测到19种植物成分。PGP显示出降低肺癌细胞增殖同时避免正常细胞死亡的潜力。PGP通过将细胞阻滞在G0/G1期并产生活性氧诱导凋亡。分别有6种和8种植物成分对PLpro和Mpro蛋白具有高亲和力。与PLpro和Mpro蛋白对接的最佳复合物5-氧代-2-吡咯烷羧酸乙酯在整个100纳秒模拟过程中显示出可能稳定的相互作用。这一发现增加了前八个命中物（对接分数≥ -1.0千卡/摩尔）预防SARS-CoV-2严重程度的可能性。这些植物成分表现出口服活性药物，违规次数不超过一次且具有类药物活性。PGP植物成分被认为是肺癌和SARS-CoV-2发病机制的双重作用剂。
