Related Experiment Video

Updated: Jun 25, 2025

Assessing Cellular Target Engagement by SHP2 PTPN11 Phosphatase Inhibitors
08:45

Assessing Cellular Target Engagement by SHP2 PTPN11 Phosphatase Inhibitors

Published on: July 17, 2020

6.2K

Targeting ATP2B1 impairs PI3K/Akt/FOXO signaling and reduces SARS-COV-2 infection and replication

Pasqualino de Antonellis1,2,3, Veronica Ferrucci1,2,3, Marco Miceli1

  • 1CEINGE Biotecnologie Avanzate, Naples, 80145, Italy.

EMBO Reports
|May 30, 2024
PubMed

Insights

A novel compound, PI-7, lowers intracellular calcium levels, hindering SARS-CoV-2 replication and COVID-19 severity. This compound shows potential as a prophylactic therapeutic agent against the virus.

Area of Science:

  • Molecular Biology
  • Virology
  • Pharmacology

Background:

  • ATP2B1 regulates cellular calcium (Ca2+) export and homeostasis.
  • Reduced intracellular Ca2+ levels may impede SARS-CoV-2 replication.
  • A specific ATP2B1 variant is linked to COVID-19 severity.

Purpose of the Study:

  • To investigate the effect of a caloxin-derivative compound (PI-7) on intracellular Ca2+ levels and SARS-CoV-2 infection.
  • To elucidate the molecular mechanism underlying PI-7's action.
  • To explore the therapeutic potential of PI-7 against COVID-19.

Main Methods:

  • Assessing the impact of PI-7 on intracellular Ca2+ levels.
  • Evaluating PI-7's efficacy in inhibiting SARS-CoV-2 infection in vitro.
  • Analyzing the involvement of the PI3K/Akt/FOXO3 signaling pathway.
  • Investigating the effect of PI-7 on ATP2B1 and ATP2A1 gene expression.

Main Results:

  • Compound PI-7 effectively reduces intracellular Ca2+ levels.
  • PI-7 demonstrates impairment of SARS-CoV-2 infection and propagation.
  • A rare ATP2B1 intronic variant correlates with COVID-19 severity.
  • PI-7 sustains ATP2B1 and ATP2A1 expression, reducing cytoplasmic Ca2+.

Conclusions:

  • Compound PI-7 exhibits potential as a prophylactic therapeutic agent for COVID-19 due to its ability to reduce intracellular Ca2+ and inhibit viral replication.
  • The mechanism involves modulation of the PI3K/Akt/FOXO3 pathway, impacting Ca2+ pump expression.
  • PI-7's lack of in vitro toxicity supports its therapeutic consideration.
Keywords:
ATP2B1Ca2+PI3K/Akt/FOXOSARS-CoV-2Transcription

More Related Videos

Genome-wide RNAi Screening to Identify Host Factors That Modulate Oncolytic Virus Therapy08:51

Genome-wide RNAi Screening to Identify Host Factors That Modulate Oncolytic Virus Therapy

Published on: April 3, 2018

9.1K
Visualization of SARS-CoV-2 using Immuno RNA-Fluorescence In Situ Hybridization05:23

Visualization of SARS-CoV-2 using Immuno RNA-Fluorescence In Situ Hybridization

Published on: December 23, 2020

6.1K

Related Concept Videos

PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
3.5K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
3.8K
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
8.8K
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
6.3K
Protein Kinases and Phosphatases02:54

Protein Kinases and Phosphatases

Proteins undergo chemical modifications that trigger changes in the charge, structure, and conformation of the proteins. Phosphorylation, acetylation, glycosylation, nitrosylation, ubiquitination, lipidation, methylation, and proteolysis are various protein modifications that regulate protein activity. Such modifications are usually enzyme-driven.
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
13.1K
ATP Synthase: Mechanism01:48

ATP Synthase: Mechanism

In animals, the mitochondrial F1F0 ATP synthase is the key protein that synthesizes ATP molecules through a complex catalytic mechanism. While the nuclear genome encodes the majority of ATP synthase subunits, the mitochondrial genome encodes some of the enzyme's most critical components. The formation of this multi-subunit enzyme is a complex multi-step process regulated at the level of transcription, translation, and assembly. Defects in one or more of these steps can result in decreased...
14.5K