College of Pharmacy and Graduates School of Pharmaceutical Sciences, Ewha W. University, Seoul 03760, Korea.
SOM Innovation Biotech SA., Baldiri Reixac, 4, 08028 Barcelona, Spain.
Int J Mol Sci. 2022 Jun 9;23(12):6468. doi: 10.3390/ijms23126468.
The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) wreaked havoc all over the world. Although vaccines for the disease have recently become available and started to be administered to the population in various countries, there is still a strong and urgent need for treatments to cure COVID-19. One of the safest and fastest strategies is represented by drug repurposing (DRPx). In this study, thirty compounds with known safety profiles were identified from a chemical library of Phase II-and-up compounds through a combination of SOM Biotech's Artificial Intelligence (AI) technology, SOMPRO, and in silico docking calculations with third-party software. The selected compounds were then tested in vitro for inhibitory activity against SARS-CoV-2 main protease (3CLpro or Mpro). Of the thirty compounds, three (cynarine, eravacycline, and prexasertib) displayed strong inhibitory activity against SARS-CoV-2 3CLpro. VeroE6 cells infected with SARS-CoV-2 were used to find the cell protection capability of each candidate. Among the three compounds, only eravacycline showed potential antiviral activities with no significant cytotoxicity. A further study is planned for pre-clinical trials.
2019 年冠状病毒病（COVID-19）的爆发是由严重急性呼吸系统综合症冠状病毒 2（SARS-CoV-2）引起的，它在全世界造成了严重破坏。尽管最近已经有了针对这种疾病的疫苗，并开始在各国向人群接种，但仍然迫切需要治疗方法来治愈 COVID-19。其中最安全和最快的策略之一是药物再利用（DRPx）。在这项研究中，通过 SOM Biotech 的人工智能（AI）技术 SOMPRO 和第三方软件的计算机对接计算，从二期及以上化合物的化学库中确定了三十种具有已知安全性的化合物。然后，对所选化合物进行了体外抑制 SARS-CoV-2 主蛋白酶（3CLpro 或 Mpro）活性的测试。在这 30 种化合物中，有 3 种（水飞蓟宾、依拉环素和普雷沙替尼）对 SARS-CoV-2 3CLpro 显示出很强的抑制活性。用 SARS-CoV-2 感染的 VeroE6 细胞来寻找每种候选药物的细胞保护能力。在这三种化合物中，只有依拉环素表现出有潜在的抗病毒活性，且没有明显的细胞毒性。计划进一步进行临床前试验研究。
