The potential effects of clinical antidiabetic agents on SARS-CoV-2

J Diabetes. 2021 Mar;13(3):243-252. doi: 10.1111/1753-0407.13135. Epub 2020 Dec 19.

Abstract
in English, Chinese

Background: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is currently posing significant threats to public health worldwide. It is notable that a substantial proportion of patients with sever COVID-19 have coexisting diabetic conditions, indicating the progression and outcome of COVID-19 may relate to diabetes. However, it is still unclear whether diabetic treatment principles can be used for the treatment of COVID-19.

Methods: We conducted a computational approach to screen all commonly used clinical oral hypoglycemic drugs to identify the potential inhibitors for the main protease (Mpro ) of SARS-CoV-2, which is one of the key drug targets for anti-COVID-19 drug discovery.

Results: Six antidiabetic drugs with docking scores higher than 8.0 (cutoff value), including repaglinide, canagliflozin, glipizide, gliquidone, glimepiride, and linagliptin, were predicted as the promising inhibitors of Mpro . Interestingly, repaglinide, one of the six antidiabetic drugs with the highest docking score for Mpro , was similar to a previously predicted active molecule nelfinavir, which is a potential anti-HIV and anti-COVID-19 drug. Moreover, we found repaglinide shared similar docking pose and pharmacophores with a reported ligand (N3 inhibitor) and nelfinavir, demonstrating that repaglinide would interact with Mpro in a similar way.

Conclusion: These results indicated that these six antidiabetic drugs may have an extra effect on the treatment of COVID-19, although further studies are necessary to confirm these findings.

背景: 由新型冠状病毒SARS-CoV-2引发的新型冠状病毒肺炎(COVID-19)在全球范围内爆发, 严重危害公众健康。值得注意的是, 相当大比例的COVID-19重症患者同时合并糖尿病, 提示COVID-19的进展和转归可能与糖尿病有关。然而, 目前尚不清楚既往的糖尿病治疗原则能否适用于COVID-19合并糖尿病患者的治疗。 方法: 我们采用计算机模拟方法, 筛选所有临床常用口服降糖药物, 以确定其对COVID-19药物研发关键靶点之一SARS-CoV-2主要蛋白酶(Mpro)的潜在抑制作用。 结果: 在所筛选的口服降糖药物中, 我们发现6种药物的对接分数高于8.0(切点), 包括瑞格列奈, 卡格列净, 格列吡嗪, 格列喹酮, 格列美脲和利格列汀, 提示它们均为潜在的Mpro抑制剂。对接分数最高的瑞格列奈与一种潜在的抗HIV和抗COVID-19药物--奈非那韦得分相近。此外, 我们发现瑞格列奈与已报道的Mpro配体(N3抑制剂)及奈非那韦具有相似的对接姿势和药效基团, 表明瑞格列奈与Mpro间的作用方式可能与N3抑制剂及奈非那韦相似。 结论: 我们的结果提示以上6种降糖药物可能对COVID-19有潜在的治疗作用, 但这些结果尚有待进一步的研究予以证实。.

Keywords: COVID-19; SARS-CoV-2; antidiabetic agents; diabetes; 新型冠状病毒。; 新型冠状病毒肺炎; 糖尿病; 降糖药物.

MeSH terms

  • A549 Cells
  • Antiviral Agents / pharmacology
  • Binding Sites
  • COVID-19 Drug Treatment*
  • Drug Discovery
  • Humans
  • Hypoglycemic Agents / pharmacology*
  • Models, Molecular
  • Molecular Docking Simulation
  • Molecular Dynamics Simulation
  • Nelfinavir / pharmacology
  • Protease Inhibitors / pharmacology
  • Viral Matrix Proteins / antagonists & inhibitors*

Substances

  • Antiviral Agents
  • Hypoglycemic Agents
  • Protease Inhibitors
  • Viral Matrix Proteins
  • membrane protein, SARS-CoV-2
  • Nelfinavir