1. Academic Validation
  2. Zika M-A Potential Viroporin: Mutational Study and Drug Repurposing

Zika M-A Potential Viroporin: Mutational Study and Drug Repurposing

  • Biomedicines. 2022 Mar 10;10(3):641. doi: 10.3390/biomedicines10030641.
Prabhat Pratap Singh Tomar 1 Miriam Krugliak 1 Anamika Singh 1 Isaiah T Arkin 1
Affiliations

Affiliation

  • 1 Department of Biological Chemistry, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Edmond J. Safra Campus Givat-Ram, Jerusalem 91904, Israel.
Abstract

Genus Flavivirus contains several important human pathogens. Among these, the Zika virus is an emerging etiological agent that merits concern. One of its structural proteins, prM, plays an essential role in viral maturation and assembly, making it an attractive drug and vaccine development target. Herein, we have characterized ZikV-M as a potential viroporin candidate using three different bacteria-based assays. These assays were subsequently employed to screen a library of repurposed drugs from which ten compounds were identified as ZikV-M blockers. Mutational analyses of conserved Amino acids in the transmembrane domain of other flaviviruses, including West Nile and Dengue virus, were performed to study their role in ion channel activity. In conclusion, our data show that ZikV-M is a potential ion channel that can be used as a drug target for high throughput screening and drug repurposing.

Keywords

Dengue virus; West Nile virus; Zika virus; drug discovery; drug repurposing; flavivirus; ion channel proteins; membrane glycoprotein; viroporins.

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