Distinct motifs in the E protein are required for SARS-CoV-2 virus particle formation and lysosomal deacidification in host cells

J Virol. 2023 Oct 31;97(10):e0042623. doi: 10.1128/jvi.00426-23. Epub 2023 Oct 13.

Abstract

Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), the virus responsible for coronavirus disease 2019 (COVID-19), has caused a global public health crisis. The E protein, a structural protein found in this virus particle, is also known to be a viroporin. As such, it forms oligomeric ion channels or pores in the host cell membrane. However, the relationship between these two functions is poorly understood. In this study, we showed that the roles of E protein in virus particle and viroporin formation are distinct. This study contributes to the development of drugs that inhibit SARS-CoV-2 virus particle formation. Additionally, we designed a highly sensitive and high-throughput virus-like particle detection system using the HiBiT tag, which is a useful tool for studying the release of SARS-CoV-2.

Keywords: ESCRT pathway; HiBiT tag; PDZ domain protein; PDZ-binding motif; envelope (E) protein; lysosomal pH; pH indicator; severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); virion secretion; virus-like particle (VLP).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs
  • COVID-19
  • Coronavirus Envelope Proteins* / metabolism
  • Humans
  • Lysosomes / metabolism
  • SARS-CoV-2* / drug effects
  • SARS-CoV-2* / metabolism
  • Viroporin Proteins / metabolism
  • Virus Release

Substances

  • Viroporin Proteins
  • envelope protein, SARS-CoV-2
  • Coronavirus Envelope Proteins