School of Pharmacy, Faculty of Health Sciences, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece.
Division of Infectious Diseases, Weill Cornell Medicine, New York, NY 10065, USA.
Molecules. 2022 Mar 28;27(7):2180. doi: 10.3390/molecules27072180.
Since the time of its appearance until present, COVID-19 has spread worldwide, with over 71 million confirmed cases and over 1.6 million deaths reported by the World Health Organization (WHO). In addition to the fact that cases of COVID-19 are increasing worldwide, the Delta and Omicron variants have also made the situation more challenging. Herein, we report the evaluation of several thiazole/thiadiazole/benzothiazole based thiazolidinone derivatives which were chosen from 112 designed derivatives by docking as potential molecules to inhibit the main protease of SARS-CoV-2. The contained experimental data revealed that among the fifteen compounds chosen, five compounds (, , , , ) showed inhibitory activity with IC within the range of 0.01-34.4 μΜ. By assessing the cellular effects of these molecules, we observed that they also had the capacity to affect the cellular viability of human normal MRC-5 cells, albeit with a degree of variation. More specifically, which is the most promising compound with the higher inhibitory capacity to SARS-CoV-2 protease (0.01 μΜ) affects in vitro cellular viability only by 57% at the concentration of 0.01 μM after 48 h in culture. Overall, these data provide evidence on the potential antiviral activity of these molecules to inhibit the main protease of SARS-CoV-2, a fact that sheds light on the chemical structure of the thiazole/thiadiazole/benzothiazole based thiazolidin-4-one derivatives as potential candidates for COVID-19 therapeutics.
自出现以来，COVID-19 已在全球范围内传播，世界卫生组织（WHO）报告的确诊病例超过 7100 万例，死亡病例超过 160 万例。除了全球 COVID-19 病例不断增加这一事实外，Delta 和 Omicron 变体也使情况更加具有挑战性。在此，我们评估了几种噻唑/噻二唑/苯并噻唑基噻唑烷酮衍生物，这些衍生物是从 112 种设计的衍生物中通过对接选择的，作为抑制 SARS-CoV-2 主蛋白酶的潜在分子。实验数据表明，在所选择的 15 种化合物中，有 5 种化合物（，，，，）表现出抑制活性，IC 范围为 0.01-34.4μΜ。通过评估这些分子的细胞效应，我们观察到它们也具有影响人正常 MRC-5 细胞细胞活力的能力，尽管存在一定的差异。更具体地说，对 SARS-CoV-2 蛋白酶具有更高抑制能力（0.01μΜ）的最有前途的化合物仅在浓度为 0.01μM 时，在培养 48 小时后对体外细胞活力的影响为 57%。总的来说，这些数据提供了这些分子抑制 SARS-CoV-2 主蛋白酶的潜在抗病毒活性的证据，这一事实阐明了噻唑/噻二唑/苯并噻唑基噻唑烷-4-酮衍生物的化学结构作为 COVID-19 治疗候选物的潜力。
