Identification of Niemann-Pick C1 protein as a potential novel SARS-CoV-2 intracellular target

Antiviral Res. 2021 Oct:194:105167. doi: 10.1016/j.antiviral.2021.105167. Epub 2021 Aug 24.

Abstract

Niemann-Pick type C1 (NPC1) receptor is an endosomal membrane protein that regulates intracellular cholesterol traffic. This protein has been shown to play an important role for several viruses. It has been reported that SARS-CoV-2 enters the cell through plasma membrane fusion and/or endosomal entry upon availability of proteases. However, the whole process is not fully understood yet and additional viral/host factors might be required for viral fusion and subsequent viral replication. Here, we report a novel interaction between the SARS-CoV-2 nucleoprotein (N) and the cholesterol transporter NPC1. Furthermore, we have found that some compounds reported to interact with NPC1, carbazole SC816 and sulfides SC198 and SC073, were able to reduce SARS-CoV-2 viral infection with a good selectivity index in human cell infection models. These findings suggest the importance of NPC1 for SARS-CoV-2 viral infection and a new possible potential therapeutic target to fight against COVID-19.

Keywords: Endosomes; Niemann-pick type C1 (NPC1); Potential therapeutic target; SARS-CoV-2; SARS-CoV-2 nucleoprotein.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biological Transport*
  • COVID-19 Drug Treatment*
  • Carbazoles / pharmacology
  • Chlorocebus aethiops
  • Endosomes / chemistry
  • Endosomes / virology*
  • HEK293 Cells
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Membrane Fusion
  • Niemann-Pick C1 Protein / analysis*
  • SARS-CoV-2 / physiology*
  • Vero Cells
  • Virus Replication

Substances

  • Carbazoles
  • Intracellular Signaling Peptides and Proteins
  • NPC1 protein, human
  • Niemann-Pick C1 Protein