You are here: Welcome » Hydroxychloroquine

Differences

This shows you the differences between two versions of the page.

Link to this comparison view

Both sides previous revisionPrevious revision
Next revision
Previous revision
Next revision
hydroxychloroquine [2022/06/07 06:52]
mathew
hydroxychloroquine [2022/09/19 01:50]
pamela [Hydroxychloroquine blocks SARS-CoV-2 entry into the endocytic pathway in mammalian cell culture]
Line 34: Line 34:
  
 There was one single rationale paper for repurposing medicine published during the early going of the pandemic that did not include any discussion at all of hydroxychloroquine, despite its being the obvious first choice. That's the one that has NIAID Director Dr. Anthony Fauci's name on it. There was one single rationale paper for repurposing medicine published during the early going of the pandemic that did not include any discussion at all of hydroxychloroquine, despite its being the obvious first choice. That's the one that has NIAID Director Dr. Anthony Fauci's name on it.
 +
 +==== Hydroxychloroquine blocks SARS-CoV-2 entry into the endocytic pathway in mammalian cell culture ====
 +
 +Published: 14 September 2022  {{ ::hcq_blocks_sars_study.png?600|}}
 +
 +Hydroxychloroquine blocks SARS-CoV-2 entry into the endocytic pathway in mammalian cell culture
 +
 +Zixuan Yuan, Mahmud Arif Pavel, Hao Wang, Jerome C. Kwachukwu, Sonia Mediouni, Joseph Anthony Jablonski, Kendall W. Nettles, Chakravarthy B. Reddy, Susana T. Valente & Scott B. Hansen 
 +
 +Communications Biology volume 5, Article number: 958 (2022) Cite this article
 +
 +
 +Abstract
 +
 +[[:Hydroxychloroquine]] (HCQ), a drug used to treat lupus and malaria, was proposed as a treatment for SARS-coronavirus-2 (SARS-CoV-2) infection, albeit with controversy. In vitro, HCQ effectively inhibits viral entry, but its use in the clinic has been hampered by conflicting results. A better understanding of HCQ’s mechanism of actions in vitro is needed. 
 +
 +Recently, anesthetics were shown to disrupt ordered clusters of monosialotetrahexosylganglioside1 (GM1) lipid. These same lipid clusters recruit the [[:SARS-CoV-2]] surface receptor angiotensin converting enzyme 2 ([[:ACE2]]) to endocytic lipids, away from phosphatidylinositol 4,5 bisphosphate (PIP2) clusters. 
 +
 +Here we employed super-resolution imaging of cultured mammalian cells (VeroE6, A549, H1793, and HEK293T) to show HCQ directly perturbs clustering of ACE2 receptor with both endocytic lipids and PIP2 clusters. In elevated (high) cholesterol, HCQ moves ACE2 nanoscopic distances away from endocytic lipids. In cells with resting (low) cholesterol, ACE2 primarily associates with PIP2 clusters, and HCQ moves ACE2 away from PIP2 clusters—erythromycin has a similar effect. 
 +
 +We conclude** HCQ inhibits viral entry through two distinct mechanisms** in high and low tissue cholesterol and does so prior to inhibiting cathepsin-L. HCQ clinical trials and animal studies will need to account for tissue cholesterol levels when evaluating dosing and efficacy. ((https://web.archive.org/web/20220915001517/https://www.nature.com/articles/s42003-022-03841-8))
  
 ===== Interactions ===== ===== Interactions =====
Back to top