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Explanations
Cole 2020 ““It concentrates in the lungs 200 to 700 times higher” than the bloodstream “
Tainling Ou 2021. known to interfere with endosomal acidification
Hcq blocks viral entry mediated by cathepsin but not TMPRSS2
Hcq+TMPRSS2 inhibitor prevents infection more than either.
Catteau. These mechanisms include inhibition of chemokines and pro-inflammatory cytokines associated with poor prognosis (interleukin-6, tumour necrosis factor-α)
Also prevention of thrombotic complications related to antiphospholipid syndrome (an autoimmune, hypercoagulable state according to Wikipedia).
Lacout. In vitro studies show that the effect of hydroxychloroquine is mainly mediated by alkalinization of the phagolysosomes,4 where it can concentrate about 1500 times more than in plasma. This effect can be obtained with low doses of hydroxychloroquine because of its long elimination half-life. High doses may therefore be useless or even deleterious because of the anti-interferon action of hydroxychloroquine,5 which may result in a more severe form of Covid-19.
Vincent 2005. In addition to the well-known functions of chloroquine such as elevations of endosomal pH, the drug appears to interfere with terminal glycosylation of the cellular receptor, angiotensin-converting enzyme 2. This may negatively influence the virus-receptor binding and abrogate the infection, with further ramifications by the elevation of vesicular pH, resulting in the inhibition of infection and spread of SARS CoV at clinically admissible concentrations.
…Chloroquine can affect virus infection in many ways, and the antiviral effect depends in part on the extent to which the virus utilizes endosomes for entry.
Dauby 2021 HCQ inhibits the production of the pro-inflammatory cytokines interleukin (IL)-6, tumour necrosis factor-alpha (TNF-α), and IL-1-β by activated macrophages (Sperber et al., 1993, Jang et al., 2006), which are notoriously associated with COVID-19 severity (Del Valle et al., 2020, Webb et al., 2020) and also the production of chemotactic cytokines involved in the recruitment of pro-inflammatory cells in the lungs (Grassin-Delyle et al., 2020).
Another?
Accapezzato, Daniele, et al. “Chloroquine enhances human CD8 + T cell responses against soluble antigens in vivo.” J Exp Med (2005) 202 (6): 817–828. Doi: https://doi.org/10.1084/jem.20051106
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Another
de Wilde
Antimicrob Agents Chemother. 2014 Aug;58(8):4875-84.doi: 10.1128/AAC.03011-14. Epub 2014 May 19.
Screening of an FDA-approved compound library identifies four small-molecule inhibitors of Middle East respiratory syndrome coronavirus replication in cell culture Adriaan H de Wilde