Scorpion-Shaped Zinc Porphyrins as Tetrafunctional TAR RNA Predators and HIV-1 Reverse Transcriptase Inhibitors

Inorg Chem. 2022 Jul 18;61(28):10774-10780. doi: 10.1021/acs.inorgchem.2c00975. Epub 2022 Jul 7.

Abstract

HIV-1 reverse transcriptase (RT) inhibitors are fundamental to the discovery and development of anti-HIV drugs. Their main target is RT, and only a tiny number of them can bind to viral RNA. In this paper, five new Zn(II) porphyrin compounds were developed with different characters. ZnTPP4 has both the appearance and the functions of a scorpion with a rigid tail and stinger to selectively hunt HIV-1 TAR RNA based on the molecular recognition of hydrogen bonds, a fierce chelicera to bite RNA by metal coordination, mighty pedipalps to grasp the bound RNA by supramolecular inclusion, and a broad body maintaining the configuration of each functional area so that they can cooperate with each other and providing accommodation space for the bound RNA. This tetrafunctional Zn(II) porphyrin is relatively nontoxic to normal cells and can produce sensitive responses for RNA. Moreover, this work offers practical construction methodologies for medication of AIDS and other diseases closely related to RT like EBOV and SARS-CoV-2.

MeSH terms

  • COVID-19*
  • HIV Reverse Transcriptase / antagonists & inhibitors
  • HIV-1*
  • Humans
  • Metalloporphyrins* / pharmacology
  • RNA, Viral
  • Reverse Transcriptase Inhibitors* / chemistry
  • Reverse Transcriptase Inhibitors* / pharmacology
  • SARS-CoV-2

Substances

  • Metalloporphyrins
  • RNA, Viral
  • Reverse Transcriptase Inhibitors
  • zinc hematoporphyrin
  • reverse transcriptase, Human immunodeficiency virus 1
  • HIV Reverse Transcriptase