The fusion of endosomes to lysosomes is also stopped so this whole process whereby the virus can enter the settle and get in can be stopped or slowed down so the way this happens again is that chloroquine increases endosomal and lysosomal ph and in doing so decreases endosomal and lysosome will functioning so it decreases or inhibits endocytosis so the second point I want to make regarding chloroquine antiviral properties is that chloroquine is a zinc ionophore there’s actually a paper published in +1 and 2014 indicating and showing evidence that chloroquine can act as a zinc ion afore that means that chloroquine can allow the entry of sank into a cell so how does chloroquine actually do this so without help zinc cannot enter into a cell it essentially bounces off of the cell membrane but with chloroquine it can actually attach to chloroquine and kor khon can actually guide it through the plasma membrane allowing zinc to enter into the cell so why is all of that important so the reason that all that is important is that there’s a study showing that zinc inhibits coronavirus and artery virus RNA polymerase activity in vitro in zinc ion affords block the replication of these viruses in cell culture and this paper was published in 2010 so normally when a virus enters specific an RNA virus there’s an RNA dependent RNA polymerase or Rd RP that RNA dependent RNA polymerase will essentially make viral RNA there’s a lot of steps involved but I won’t get into all of those steps here nonetheless this our TRP will produce viral RNA it replicates the virus however when there is chloroquine and zinc around these can cross over the plasma membrane together again the chloroquine acts as a zinc ion a– for allowing zinc and chloroquine to enter into the cell we talked about this before chloroquine has its effects on the N is ohms and lysosomes but this mechanism here more specifically has to do with the zinc so as the chloroquine brings in zinc zinc concentrations in the cytosol increase and the zinc can then act to inhibit this RNA dependent RNA polymerase action so it prevents that polymerase from making viral RNA so it essentially stops the virus from replicating its genetic code so it stops making viral RNA so this study that I just showed actually shows that as zinc concentrations increase viral RNA decreases if you want to check out more on that please check out that paper and look at some of their data they show some interesting data so again as zinc concentrations increase viral RNA decreases that is the second mechanism in the third point I want to make about chloroquine in hydroxy Corwin’s antiviral properties is based on this newest article that is being published in April of 2020 so this article is entitled structural and molecular modeling studies reveal a new mechanism of action of chloroquine in hydroxychloroquine against SARS CoV 2 infection so what does this paper show so it all has to do with the cell membrane around the ACE 2 receptor there’s actually something called psionic acid that is attached to the cell membrane that is usually pretty close to the 8th – receptor although it can be on much of the cell membrane it’s Salik acid is essentially just a little piece of sugar and the spike protein the s protein on the SARS CoV 2 virus can actually bind to the silac acid as well so these silac acid residues actually can act like little receptors for the S proteins on the corona virus as well so what this paper shows is that chloroquine in hydroxychloroquine can actually bind to these silac acid residues preventing the s protein on the SARS CoV 2 virus from binding to the South acid and essentially preventing the binding of the virus to the ACE 2 receptor as well so the way that chloroquine binds to the sonic acid it actually prevents proper binding of the SAR co v 2 virus to the ACE 2 receptor so this is another mechanism by which chloroquine and hydroxychloroquine can inhibit the SAR CoV 2 virus from actually infecting a host cell so again the three ways that I talked about in this lesson are that chloroquine and hydroxychloroquine can alkalinize endosomes in lysosomes preventing endocytosis or preventing this process from occurring can also allow the influx of zinc into the host cell increasing concentrations can lead to inhibition of the RNA dependent RNA polymerase and preventing viral RNA from being formed the third point is that chloroquine hydroxychloroquine can bind to silac acid preventing the s protein on SAR Co V 2 from properly binding to the East 2 receptor so these are the few mechanisms by which chloroquine and I’d Rock sakura-con have been shown to have some antiviral effects at least in vitro again the big disclaimer here is that all of this has been shown in vitro essentially in cell culture in a petri dish so this is far from being shown in human clinical trials so keep that in mind when we look at this evidence so far.

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