Yuan et al.: "Hydroxychloroquine blocks SARS-CoV-2 entry into the endocytic pathway in mammalian cell culture"; 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.
SOURCE:
https://www.nature.com/articles/s42003-022-03841-8
‘In order to test a membrane-disruptive mechanism for HCQ inhibition of SARS-CoV-2 viral entry, we compared HCQ to anesthetics (tetracaine and propofol) which are known to be membrane-disruptive. HEK293T cells overexpressing ACE2 were infected with a retrovirus pseudotyped with the SARS-CoV-2 spike protein (SARS2-PV). A segment of the spike protein binds to ACE2 and recapitulates viral entry47,48. A luciferase encoded in the pseudotyped virus is then used to quantitate viral entry (Fig. 1b–d).
Treatments with HCQ, tetracaine, and propofol all robustly reduced SARS2-PV entry into HEK293T cells overexpressing ACE2 (Fig. 1b). The cells were first treated with drugs (50 µM) for 1 h, then the drugs were removed. After the treatment and subsequent drug removal, SARS2-PV was applied such that the virus was never exposed to the drugs, thus avoiding potential direct effects of cholesterol on the viron. HCQ had the greatest effect on viral inhibition with almost a 90% reduction in SARS2-PV luciferase activity (Fig. 1b). We used 50 µM since that concentration was previously shown to be the minimum concentration that fully inhibited viral entry3.’
So, in short, HCQ is quite effective at treating COVID. Good to know, 2.5 years and a million deaths later. Too bad Fauci and friends withheld this life-saving medicine from the world.
They already knew in 2005 that it might work: Chloroquine is a potent inhibitor of SARS coronavirus infection and spread https://doi.org/10.1186/1743-422X-2-69
Yet there came the self-declared "fact checkers" basically stating this is wrong because it's a different virus and it's also wrong because the 3-letter-agencies said so: https://www.reuters.com/article/uk-factcheck-chloroquine-sars-covid-19/fact-check-chloroquine-sars-study-does-not-prove-hydroxychloroquines-effectiveness-against-covid-19-idUSKCN2512A7
This is how The Science™ works nowadays.