COVID: chloroquine's antiviral effects

for those interested in the pharmacology of chloroquine in the context of SARS-CoV-2, see https://reader.elsevier.com/reader/sd/pii/S0924857920300881?token=B8320F2D7609180B3203A21CD0B1DC787CBE966357763D4CBB12AEEAD8F7E0BFC9E9508DFE1C4D07455BE25148893E08 , sent to me by julita mir.

this review indicates that chloroquine/hydroxychloroquine might have several different mechanisms of antiviral action that could impede SARS-CoV-2 

-- chloroquine has widespread antiviral effects (including SARS-CoV-1, hiv, zika, dengue, hepatitis B, hsv...)  found in in-vitro tests.  

--for SARS-CoV-2, there are suggestive data that chloroquine:
    --can inhibit a pre-entry step of the viral cycle: interfering with viral particles binding to ACE2 receptors
    --can impair another early step in viral replication: interfering with pH-dependent endosome-mediated viral entry: prevention of endocytosis and/or elevating endosomal pH (a pH-dependent mechanism for entry was reported for SARS-CoV-1)
    --can interfere with post-translational modification of viral proteins (involving proteases and glycosyltransferases)
    --can impair viral protein maturation by pH modulation
    --can directly affect the immune system by inhibiting activation of the p38 mitogen-activated protein kinase, which frequently is required by viruses in their replication cycle. 
    --and, chloroquine/hydroxychloroquine are well-known immunomodulators that can affect the anti-inflammatory response (hence, activity in rheumatoid arthritis, lupus)

So, interesting article. Lots of the biochemical details are beyond us mere mortal clinicians, but the array of potential antiviral targets is impressive and adds to the likelihood of chloroquine and hydroxychloroquine actually working with SARS-CoCV-2.  But, of course, the real test is whether it actually does work. Hopefully to be determined soon. and the question of inhibiting early steps of viral entry into target cells does raise the potential for Covid-19 prevention (also being studied)

geoff​

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