Although several pharmacological agents are under investigation to be repurposed as therapeutic against COVID-19, not much success has been achieved yet. So, the search for an effective and active option for the treatment of COVID-19 is still a big challenge. The Spike protein (S), RNA-dependent RNA polymerase (RdRp), and Main protease (Mpro) are considered to be the primary therapeutic drug target for COVID-19. In this study we have screened the drugbank compound library against the Main Protease. But our search was not limited to just Mpro. Like other viruses, SARS-CoV-2, have also acquired unique mutations. These mutations within the active site of these target proteins may be an important factor hindering effective drug candidate development. In the present study we identified important active site mutations within the SARS-CoV-2 Mpro (Y54C, N142S, T190I and A191V). Further the drugbank database was computationally screened against Mpro and the selected mutants. Finally, we came up with the common molecules effective against the wild type (WT) and all the selected Mpro. The study found Imiglitazar, was found to be the most active compound against the wild type of Mpro. While PF-03715455 (Y54C), Salvianolic acid A (N142S and T190I), and Montelukast (A191V) were found to be most active against the other selected mutants. It was also found that some other compounds such as Acteoside, 4-Amino-N- {4-[2-(2,6-Dimethyl-Phenoxy)-Acetylamino]-3-Hydroxy-1-Isobutyl-5-Phenyl-Pentyl}-Benzamide, PF-00610355, 4-Amino-N-4-[2-(2,6-Dimethyl-Phenoxy)-Acetylamino]-3-Hydroxy-1-Isobutyl-5-Phenyl-Pentyl}-Benzamide and Atorvastatin were showing high efficacy against the WT as well as other selected mutants. We believe that these molecules will provide a better and effective option for the treatment of COVID-19 clinical manifestations.

尽管正在研究几种药物以重新用于治疗 COVID-19，但尚未取得太大成功。因此，寻找有效且积极的治疗COVID-19的选择仍然是一个巨大的挑战。刺突蛋白（S）、RNA依赖性RNA聚合酶（RdRp）和主蛋白酶（Mpro）被认为是COVID-19的主要治疗药物靶点。在这项研究中，我们针对主要蛋白酶筛选了药物库化合物库。但我们的搜索并不仅限于 Mpro。与其他病毒一样，SARS-CoV-2 也获得了独特的突变。这些靶蛋白活性位点内的这些突变可能是阻碍有效候选药物开发的重要因素。在本研究中，我们确定了 SARS-CoV-2 Mpro 内的重要活性位点突变（Y54C、N142S、T190I 和 A191V）。此外，药物库数据库针对 Mpro 和选定的突变体进行了计算筛选。最后，我们提出了对野生型（WT）和所有选定的 Mpro 有效的常见分子。研究发现，Imiglitazar 是对抗野生型 Mpro 最活跃的化合物。而 PF-03715455 (Y54C)、丹酚酸 A（N142S 和 T190I）和孟鲁司特 (A191V) 被发现对其他选定的突变体最有活性。还发现一些其他化合物，例如 Acteoside、4-氨基-N-{4-[2-(2,6-二甲基-苯氧基)-乙酰氨基]-3-羟基-1-异丁基-5-苯基-戊基}-苯甲酰胺，PF-00610355，4-氨基-N-4-[2-(2,6-二甲基-苯氧基)-乙酰氨基]-3-羟基-1-异丁基-5-苯基-戊基}-苯甲酰胺和阿托伐他汀对 WT 以及其他选定的突变体表现出高效。我们相信这些分子将为治疗COVID-19临床表现提供更好、更有效的选择。