HC Q in vitro study
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In Vitro
In Vitro
Hoffmann et al., Nature, (2020), doi:10.1038/s41586-020-2575-3 (Peer Reviewed) (In Vitro) (not included in the study count)
Ch loroquine does not inhibit infection of human lung cells with SARS-CoV-2
The title of this paper does not appear to match the results. Fig. 1b @100uM shows C Q results in a ~4.5 fold decrease (on a linear scale) in extracellular virus, p=0.05, after 24 hours (we do not see the supplementary data at this time so this is estimated from the graph). This decrease may continue if examined over longer time periods. Fig. 1a shows a ~45-50% entry inhibition @100uM for HC Q/C Q (p=0.0005/0.0045), ~10-30% @10uM (p=0.13/0.99). Inhibition is significantly better with Vero cells.
In vitro study of C Q and HC Q inhibition of SARS-CoV-2 into Vero (kidney), Vero-TMPRSS2, and Calu-3 (derived from human lung carcinoma) cells.
Although there are several theories on how HC Q may help with COVID-19, authors do not consider the most common theory where HC Q functions as a zinc ionophore, facilitating significant intracellular concentrations of zinc. Zinc is known to inhibit SARS-CoV RNA-dependent RNA polymerase activity, and is widely thought to be important for effectiveness with SARS-CoV-2 [1].
Calu-3 is one of many cell lines derived from human lung carcinomas [2]. Calu-3 cells resemble serous gland cells. They do not express 15-lipoxygenase, an enzyme specifically localized to the surface epithelium, but they do express secretory component, secretory leukocyte protease inhibitor, lysozyme, and lactoferrin, all markers of serous gland cells. [3] note that the absence of systemic inflammation, circulatory factors, and other paracrine systemic influences is a potential limitation of the isolated cell system.
RT-PCR is used, we note that nucleic acid may persist even after the virus is no longer viable [4].
It is unclear how the authors conclude "C Q does not block SARS-CoV-2 infection of Calu-3" cells, when the results show statistically significant inhibition at higher concentrations.
Further, it is unclear how the authors go from these results in one specific type of pulmonary adenocarcinoma cells that resemble serous gland cells, in vitro, into the title of the paper which claims no inhibition in lung cells.
Further, it is unclear how another leap is made to "will not be effective against COVID-19" given the multiple theories of HC Q/C Q effectiveness.
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