Summary of project PR002099
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR002099. The data can be accessed directly via it's Project DOI: 10.21228/M89C1V This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Project ID: | PR002099 |
| Project DOI: | doi: 10.21228/M89C1V |
| Project Title: | PIP4K2C inhibition reverses autophagic flux impairment induced by SARS-CoV-2 |
| Project Type: | Lipidomics of Human lung epithelial cells |
| Project Summary: | In this study, we calculated the peak area abundance of phosphoinositide lipids in SARS-Cov2 infected, uninfected and dual lipid kinase (PIP4K2C and PIKfyve) inhibitor treated (RMC-113,) (PI, PIP, PIP2 and PIP3) Human lung epithelial cells. We discovered PIP4K2C’s (Phosphatidylinositol-5-phosphate 4-kinase, type II, gamma) roles in SARS-CoV-2 entry, RNA replication, and assembly/egress, validating it as a druggable antiviral target. Integrating proteomics, single-cell transcriptomics, and functional assays revealed that PIP4K2C binds SARS-CoV-2 proteins and regulates virus-induced impairment of autophagic flux. Reversing this autophagic flux impairment is a mechanism of antiviral action of RMC-113(dual lipid kinase inhibitor (PIP4K2C and PIKfyve). These findings reveal virus-induced autophagy regulation via PIP4K2C, an understudied kinase, and propose dual inhibition of PIP4K2C (Phosphatidylinositol-5-phosphate 4-kinase, type II, gamma) and PIKfyve (a FYVE finger-containing phosphoinositide kinase) as a candidate strategy to combat emerging viruses. |
| Institute: | Stanford School of Medicine |
| Department: | medicine |
| Laboratory: | Einav lab |
| Last Name: | mishra |
| First Name: | manjari |
| Address: | 3332 middlefield road |
| Email: | manjari1@stanford.edu |
| Phone: | 6503849709 |
| Funding Source: | NIH |
| Publications: | https://www.biorxiv.org/content/10.1101/2024.04.15.589676v1.full |
| Contributors: | Marwah Karim, Manjari Mishra, Chieh-Wen Lo, Sirle Saul, Halise Busra Cagirici, Do Hoang Nhu Tran, Aditi Agrawal, Luca Ghita, Amrita Ojha, Michael P. East, Karen Anbro Gammeltoft, Malaya Kumar Sahoo, Gary L. Johnson, Soumita Das, Dirk Jochmans, Courtney A. Cohen, Judith Gottwein, John Dye, Norma Neff, Benjamin A. Pinsky, Tuomo Laitinen, Tatu Pantsar, Antti Poso, Fabio Zanini, Steven De Jonghe, Christopher R M Asquith, Shirit Einav |
Summary of all studies in project PR002099
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST003388 | RMC-113 (dual-lipid kinase inhibitor, PIKfyve, PIP4K2C) alters the phosphoinositide regioisomer signature by advanced lipidomics analysis | Homo sapiens | Stanford University | MS | 2024-08-28 | 1 | 4 | Uploaded data (1.3M)* |
