[Role of cyclophilin A during coronavirus replication and the antiviral activities of its inhibitors]

Sheng Wu Gong Cheng Xue Bao. 2020 Apr 25;36(4):605-611. doi: 10.13345/j.cjb.200049.
[Article in Chinese]

Abstract

Cyclophilin A (CypA) is a widely distributed and highly conserved protein in organisms. It has peptidyl-prolyl cis/trans isomerase activity and is a receptor for cyclosporin A (CsA). Coronaviruses are enveloped, single-stranded, positive-sense RNA viruses. Seven types of coronaviruses are currently known to infect humans, among which SARS-CoV, MERS-CoV, and SARS-CoV-2 are fatal for humans. It is well established that CypA is essential for the replication of various coronaviruses such as SARS-CoV, CoV-229E, CoV-NL63, and FCoV. Additionally, CsA and its derivatives (ALV, NIM811, etc.) have obvious inhibitory effects on a variety of coronaviruses. These results suggest that CypA is a potential antiviral target and the existing drug CsA might be used as an anti-coronavirus drug. At the end of 2019, SARS-CoV-2 raged in China, which seriously theatern human health and causes huge economic lases. In view of this, we describe the effects of CypA on the replication of coronaviruses and the antiviral activities of its inhibitors, which will provide the scientific basis and ideas for the development of antiviral drugs for SARS-CoV-2.

亲环素 A (CypA) 是一种在生物界中广泛分布,并具有高度保守性的蛋白质,具有肽基脯氨酰顺/反异构酶活性,是免疫抑制药物环孢素A (CsA) 的细胞内受体。冠状病毒是具有包膜的、单股正链RNA 病毒,目前已知有7 种冠状病毒可以感染人类,其中包括致命的SARS-CoV、MERS-CoV 以及新型冠状病毒 (SARS-CoV-2)。已有研究表明,CypA 在SARS-CoV、CoV-229E、CoV-NL63 以及FCoV 等多种冠状病毒的复制中是必不可少的,而且CypA 的抑制剂CsA 及其衍生物 (ALV、NIM811 等) 对多种冠状病毒具有明显的抑制作用,暗示CypA 是潜在的抗冠状病毒药物靶点,CsA 这种老药有可能是一种抗冠状病毒的药物。2019 年底,新型冠状病毒突然肆虐中国,严重威胁人民生命健康并造成巨大经济损失。鉴于此,文中介绍了CypA 对冠状病毒复制的影响,并阐述了其抑制剂的抗病毒作用,旨在为抗新型冠状病毒药物的研发提供科学依据及思路。.

Keywords: SARS-CoV-2; coronaviruses; cyclophilin A; cyclosporin A.

Publication types

  • Review

MeSH terms

  • Antiviral Agents / pharmacology*
  • Antiviral Agents / therapeutic use
  • Betacoronavirus / drug effects
  • Betacoronavirus / growth & development
  • COVID-19
  • Coronavirus / drug effects*
  • Coronavirus / growth & development*
  • Coronavirus Infections* / drug therapy
  • Coronavirus Infections* / epidemiology
  • Coronavirus Infections* / virology
  • Cyclophilin A / antagonists & inhibitors*
  • Cyclosporine / chemistry
  • Cyclosporine / pharmacology*
  • Cyclosporine / therapeutic use*
  • Humans
  • Pandemics*
  • Pneumonia, Viral* / drug therapy
  • Pneumonia, Viral* / epidemiology
  • Pneumonia, Viral* / virology
  • SARS-CoV-2
  • Severe acute respiratory syndrome-related coronavirus / drug effects
  • Severe acute respiratory syndrome-related coronavirus / growth & development
  • Virus Replication / drug effects

Substances

  • Antiviral Agents
  • Cyclosporine
  • Cyclophilin A