Link to featured video.
Link to Wefwafwa’s channel.
(he needs more subscribers).
Link to support Wefwafwa’s work in Africa.
Drugs Shown to Inhibit SARS-CoV-2 in COVID-19
Disease: Comparative Basic and Clinical Pharmacology of Molnupiravir and Ivermectin.
https://www.linkedin.com/in/leslie-adesuyi-ajayi-md-phd-fbpharmacols-fwacp-69154a38/. There are still many nations where vaccines are not yet widely available, .
There is a gradual shift in focus, to antiviral drugs, .
Active treatment of new SARS-CoV-2 infections.
Post -vaccination breakthrough COVID-19 cases.
The two ways to get new drugs.
Develop novel antiviral drugs for SARS-CoV-2 .
Repurpose existing FDA -approved drugs to treat COVID-19.
Ivermectin is the most studied “repurposed” medication globally, .
in randomized clinical trials, retrospective studies and meta- analyses. .
Molnupiravir and Ivermectin Anti-SARS- CoV-2 Mechanisms, Pharmacokinetics and Pharmacodynamics .
Molnupiravir is a broad spectrum antiviral agent against SARS- CoV-2, SARS-CoV,.
seasonal or pandemic influenza and MERS corona virus.
Ivermectin is an FDA-approved, WHO essential drug used as broad spectrum antiparasitic, antibiotic .
and which has demonstrated broad spectrum antiviral activity against RNA viruses, including HIV, Zika, MERS corona virus.
The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro. https://www.sciencedirect.com/science/article/pii/S0166354220302011.
5000-fold inhibition of SARS-CoV-2, (99.98% at 48 hours.
The inhibitory concentration IC50 of Molnupiravir shows it to be a more potent anti-SARS-CoV-2 agent, compared to Ivermectin in vitro. .
Both molnupiravir and ivermectin are well absorbed after oral dosing.
Tmax of molnupiravir being 1-1.75 hours,.
With a half life of 7 hours.
Tmax of ivermectin is 4-6 hours.
Very long half life of 81-91 hours.
Ivermectin, being lipophilic has a large volume of distribution.
Ivermectin has the ability to accumulate in the lungs.
The anti-SARS-CoV-2 actions, both of molnupiravir and ivermectin, are dose and concentration dependent.
Molnupiravir active metabolite (NHC-5’ Triphosphate), acts as a competitive alternative substrate for viral RNA.
causing viral mutagenesis or mutations, which leads to viral error catastrophe and extinction of replication.
There is some concern about the safety of NHC -nucleoside triphosphate, which is also mutagenic to mammalian cells.
Ivermectin, multifarious actions, .
Binding to SARS-CoV-2 spike protein S. Reducing cell entry via human ACE2 receptors .
Reducing viral transcription.
Inhibition of cytokine production and inflammation.
(not yet been shown for molnupiravir) .
Complimentary pharmacokinetics and pharmacodynamics of the drugs.
May be additive or synergistic.
This should be further investigated in anti-SARS- CoV-2 antiviral combination therapy..
A combination of molnupiravir with Ivermectin putatively, in effects on RdRP or cytokine release. .
The cost for a package of 100 tablets of 3 mg ivermectin is $2.96..
Say, 12mg per day for 5 days = $0.53.
https://www.who-umc.org/vigibase/vigibase/. . .
https://pubmed.ncbi.nlm.nih.gov/34145166/. For deaths, average risk ratio 0.38, (62% benefit) (moderate-certainty evidence.
Early treatment .
Main results, Treating people in hospital with COVID-19.
We don't know whether ivermectin compared with placebo or usual care, 28 days after treatment:– .
leads to more or fewer deaths.
worsens or improves patients' condition assessed by need for ventilation or oxygen.
increases or reduces unwanted events.
We don't know whether ivermectin leads to more or fewer deaths compared with no drug
0:00:30 | well a warm welcome to today’s talk
and as you can see it’s pretty dark outside it’s rained here for days autumn as well and truly arrived now of course we did a video a couple of days ago on the new anti-viral from merc called multnol peruvia that’s seeking fda and international approval at the moment and had about 6 000 questions on relating modern this new anti-viral drug to potential older anti-viral drugs so that’s what this is about so we’re going to compare mull nor peruvia with Ivermectin now I’m aware
0:01:00 | that this issue is sensitive shall we
say so everything I say is going to be based on evidence and I’m going to show you the evidence and where the evidence is unclear I’m going to be upfront about that and tell you about that now we’re going to start off by looking at this paper here so this recently published paper now this is published from austin publishing which is a peer-reviewed publishing group drugs shown to inhibit size coronavirus 2 and covered 19 disease comparative basic and clinical
0:01:30 | pharmacology of mulnor pyravir and Ivermectin so
this is a brief paper but covers quite a lot of key points and does quite a few interesting comparisons now because we’re very keen to look at validity here I did check up the main author and he is a professor of medicine in texas with a specialist expertise adjunct professor of medicine at baylier college of medicine with particular expertise of course as you would expect in pharmacology
as we try and check what we’re saying as we go through right there’s still many nations where vaccines are not widely available except in fact vaccine roll out is patchy around the world at best there’s a gradual shift to focus to antiviral drugs now if there was good quality anti-viral drugs then countries that are still waiting to be vaccinated the impact could be much less because they would have antiviral drugs
0:02:30 | potentially to prevent the transmission of the
disease and to treat it should it occur because the end the analogy i’ve used many times if you’ve watched this channel is bubonic plague which killed people in the black death by the well it killed huge percentages of the population in the past but now we just treat it with antibiotics we don’t vaccinate against it we just treat it when it arises so we need this as a an adjunct to vaccination is the thinking of this paper so adjunctive chemo prophylaxis now chemo means it’s a chemical a drug
0:03:00 | prophylaxis means to prevent adjunctive means it’s
as well as the vaccine so we don’t want to get into this argument do we want antivirals or do we want the vaccines I want both I’m pro-vaccine I’m also pro-antiviral we don’t want divisions into different camps that is not helpful we want to examine what the truth is so the active treatment of the sars coronavirus two infections so for adjunctive preventative treatment and for active treatment as well both
0:03:30 | would be brilliant we want to stop
people getting it and we certainly want to treat them when they do get sick if we can and also for post-vaccine breakthrough cases which okay that there are some issues with that at the moment so we’ll accept that two ways to get new drugs develop novel antivirals so new ones or repurpose existing drugs now there’s a lot of repurposing of drugs going on in the history of medicine if we take aspirin for example I mean aspirin comes from willow bark and it was first used to treat fevers
0:04:00 | but then people realized it was a
painkiller it was analgesic and then people realized it made your platelets less sticky so we give we give it as an antiplatelet blood thinning drug as well and you know there’s lots of examples of this where one drug was developed for one thing and it finds out to be useful for another thing so repurposing wouldn’t be at all surprising as well worth looking at of course an example from this pandemic that’s unambiguous is steroids they’ve been repurposed so steroid drugs that have been using all my career so at least for the last 40 odd years
0:04:30 | and then we repurposed it to treat
the inflammatory complications of covid19 so that’s not surprising so Ivermectin is the most studied repurposed drug according to this paper just quoting what the paper says in random randomized clinical trials retrospective studies and meta-analyses this paper is claiming and do do read the whole paper for yourself it some of the biochemistry is a bit technical but you should you should kind of get the get the gist of it it’s not totally inaccessible although it is
0:05:00 | a scientific paper monopovia and ibermectin antiservice2
mechanisms pharmacokinetics is the way that the body interacts with the drug and pharmacodynamics is the way that the drug works on the body to have an effect whether that effect is good or that effect is bad so a muller period broad spectrum antiviral agent again size coronavirus two and I believe it was first developed to treat influenza so it’s got action against seasonal seasonal pandemic influenza and also
and the data we looked at released from merck does show that peruvia is active against all of the variants so far that the study was able to incorporate anyway all of the variants of them of covert 19. so ivan mechtin is an fda approved who essential drug as a broad spectrum anti-parasitic and antibiotic he’s saying and of course it won the nobel prize
0:06:00 | the the two discoverers won the nobel
prize in two co won the nobel prize in 2015 as Ivermectin has revolutionized the human treatment of parasitic disease around the world a direct quote from the paper and which has demonstrated broad spectrum anti-viral activity against rna viruses including hiv zika mers coronavirus so that is the quote from that paper check it out
0:06:30 | for yourself the fda approved drug Ivermectin
inhibits the replication of sars coronavirus to in vitro now this means in experimental circumstances and this again is not ambiguous this goes way back to what paper was this this goes way back to this paper here one of the early papers from 2020 from australia the fda approved a guy remember inhibits replication of size coronavirus 2 in vitro not in vevo this is looking at in vitro
0:07:00 | so that is there and I think
this is pretty well I think we can say that’s pretty well accepted science now no one seems to debate that particular point anymore five thousand fold inhibition of science coronavirus ii it got rid of 99.98 of viable particles in the first 48 hours remember that is the Ivermectin in vitro now the inhibitory con inhibitory concentration so-called ic50 of multnor peruvian it shows to be more potent because you
0:07:30 | need less more more peripheral in the
tissues according to this data here to get the therapeutic effect so that would be a dosing thing and that would be the timing of the the interventions but it’s looking like the mullen or purview is working on lower tissue concentrations but it’s a bit more complicated as we’ll see both north peruvia and ivory mexican are well absorbed orally so you take them by math it’s the big example the the big selling point of the new multnomah peruvian you don’t need to give it viral
0:08:00 | intravenous infusion like you do the monoclonal
antibodies t-max that’s the t-max is the time it takes to get to maximum plasma concentrations for multnomah purvey it takes about one to two hours to get some maximum concentration with ivanka and it takes a bit longer four to six hours you need to give two doses of more periviera a day because the half-life the time taken to excrete half of the given dose of the drug from the plasma is seven hours whereas I haven’t mentioned it’s long now this paper quotes 81 to 91 hours now
0:08:30 | this is surprisingly long I had thought
it was around 17 hours but I’m just quoting what this paper says and being lipophilic has a large volume of distribution in other words it dissolves in fatty tissues and of course the cell membranes of the body are fatty tissue so it’s able to diffuse into a very wide number of cells the Ivermectin is hypomethane has the ability to accumulate in the lungs which of course is one of the main target organ for sars coronavirus ii so it’s not just about
0:09:00 | the half-life of the ivox and it
seems to accumulate in the tissues in the lungs and as far as we understand from my conversation with vets it stays there for a long period of time so it can have a long acting effect locally in the lungs so you could end up with higher concentrations in the lungs than other places which of course in terms of treating severe acute respiratory distress syndrome is exactly where you want it so the normal sort of kinetics of this of drugs is the little change it’s not just half-life it’s where the drug
0:09:30 | accumulates in the tissues the drug accumulates
in that we would need to take account of the antisars coronavirus two actions both of no periphery and Ivermectin are dose and concentration dependent as we’ve said malno pirivia is is an is an active it’s so that it’s it’s what you call a pro drug the molal pyruvate is given it’s converted I believe in the liver into the active substance now this isn’t uncommon again in pharmacology so for example if you take take codeine for example the reason that codeine is a painkiller
0:10:00 | is the codeine goes to the liver
and the liver converts it to morphine so it’s actually the morphine that’s having the the pain killing effect so again this is not surprising drugs and drug metabolites are well recognized in pharmacology so the active metabolite nhc5 try try triphosphate acts as a competitive alternative substrate for viral rna now i’ll tell you what I understand by this so the the
0:10:30 | rna is made of bases and the
the this acts so so it’s made of these these four bases to make the new rna molecule which of course is what the the the virus runs on it runs on rna whereas on dna and this is like a substrate that gets into the new rna molecule and basically sabotages the molecule now that’s the way I understand it at the moment if my understanding improves I will certainly get you on that but it’s like a competitive substrate so instead of having the proper substrate that the virus would like you get this monopovia substrate
0:11:00 | and that kills the that goes on
to cause mutations in the virus and makes the virus the new viral particles non-viable so it stops replication of the virus that’s my understanding at the moment as I say if it’s wrong or it needs corrected or purified i’ll we’ll get back on that but that’s my outstanding just now causes viral mutagenesis so it causes mutation in the virus mutations which lead to viral error catastrophe and extinction of replication in other words it can’t
0:11:30 | reproduce with this dodgy stuff inside it
now the direct quote from this paper there’s some concern about the safety of this metabolite which also is mutagenic to mammalian cells now the merck announcement said yesterday that that wasn’t a problem this paper suggests that it needs I think well at least it needs looking into so the idea here is if it stops the normal replication of rna is it going to stop the normal replication of our own dna so that’s a diary all I’m saying is
0:12:00 | that’s a direct quote from the paper
of course all the data from merck as we understand it now is with the fda and the european medicine agency and all the regulatory authorities around the world they’ve got probably about a thousand times more information than we have but that’s all we can say from public domain data at the moment they will have to make adjudications on that but merck’s statement yesterday indicated that this wouldn’t be a problem but this paper indicates that it needs to be considered at least Ivermectin works in different ways it
0:12:30 | binds to the spike protein to stop
the spike protein going into the cell effect it affects the ace2 receptor to stop the virus going to the cell as well and it reduces the viral transcription in other words it stops the production of new viral rna according to this again according to this paper that we’re analyzing today so a wide variety of actions and also Ivermectin is anti-inflammatory as well which is why people are studying its potential efficacy against long covert
0:13:00 | inhibits cytokine production it’s in the pro-inflammatory
cytokines that cause the inflammation monopoly doesn’t seem to be anti-inflammatory but we await further data so complementary pharmacokinetic and pharmacology of the drug might give rise to an additive or a synergistic effect now what this is saying is these two drugs work in different ways so if they were given together you might get an effect of two from the Ivermectin an effective two from the mole nor pyrage or perivia giving a a total action of
0:13:30 | four but then again it might be
synergistic so you might get an effect of two from the normal pyramid effect of two from the Ivermectin but that might end up in an eight times improvement it could be a synergistic effect don’t know work hasn’t been done as far as we are aware certainly not published that i’ve seen so could be given together basically is what this paper is suggesting could be investigated in fact they say this should be further investigated in an anti science
this study is suggesting as a possible combination treatment a combination of multiplier with livermectin maybe we don’t know so so that’s possibility now what we are firm about is the cost now so far the the mono piravia is about 700 of course so it’s I think as far as I know it’s bd that’s twice a day for for five days
0:14:30 | so that would be a total of
10 capsules and that would equal 70 per capsule that’s the price that the u.s government seems to have paid so far what the eventual price will be merck has said the price will be different depending on what country can afford what the country can afford which is good of course so that’s kind of the price so far looking about 700 of course now according to the world health organization the cost of a packet have a hundred immediate tablets is
0:15:00 | three milligram tablets is two dollars and
ninety six cents so say we took 12 milligrams a day for five days that would give a total cost of treatment of 53 cents which is about 45 english pennies so that is the comparative cost of the two drugs now the comparative safety of course we don’t know yet because we don’t know the safety of mullen or peruvia this is from let me show you where this is from
0:15:30 | this is from veggie base which apparently
picks up most of the world’s prescriptions it’s a obsolete monitoring center combined with a who and all the who and all sorts of things from the place in sweden where it first started and it’s looking at the risks and side effects of drugs you can check it out there and it’s absolutely great because you can actually go into this and you can look up the safety profile of any drug it really is quite an impressive really has quite an impressive
0:16:00 | quite impressive database this so let me
just give you a couple examples from it I have a mectin 3.7 billion doses i’ve been given 3.7 billion doses given to human beings this is not counting animal data that’s 3.7 billion doses have been given to people and the adverse events reported at 5 000 693 if we compare that with another common drug like amoxicillin where there’s been 136 000 reported adverse
0:16:30 | events in another common drug like ibuprofen
which is the aspirin type anti-inflammatory we call it briefing in this country hundred and sixty five thousand adverse events reported so from that we see that ivanka’s got a very low amount of adverse events reported compared to other a couple of compared to those couple of other common pharmaceuticals and as I say of course we don’t have this data yet for more north because this is post-release data how well do they work the efficacy
0:17:00 | well we know that the multnomah period
is about 50 reduction in deaths and hospitalizations from yesterday so we can say roughly malnour peruvia preventing 50 of hospitalizations and deaths those studies being done in people that had at least one risk factor for hospitalization or death being treated early I have a mectin so so saying about fifty percent efficacy present hospitalization and death for the modern or pyravirus kind of the figure
0:17:30 | that we’re working on from yesterday’s video
day before’s video I have a mectin now this paper here this is the test test lorry paper she’s saying a 62 benefit from her meta-analysis with a moderate certainty evidence do look at this amazing meta ongoing meta analysis here now this is lifetime so for example when there was a question over the efficacy or the the validity really of the data from an elgaza elgazar study I think it was in egypt
0:18:00 | they simply took it out and recalculated
it so they were doing this in an ongoing basis so they’re saying the early treatment so that would be like zero would be there one making no difference would be there and so they’re saying that this is like like about you know it’s about about point point three isn’t it so yeah it’s a sixty-six percent improvement they’re saying from early treatment late treatment with Ivermectin they’re claiming a sixty forty percent improvement from their analyses and
0:18:30 | prophylaxis they suggested 86 improvement so two
very positive meta analyses there on the efficacy of Ivermectin look at them for yourself they are there they are accessible i’ve given you the links a counter argument comes from the cochrane library which does a lot of peer reviews main results treating people in hospital with covered 19. now I have mentioned this before from the cochrane library I think this was largely carried out by german academics and all I’m going to do because i’ve
0:19:00 | gone on for some time now is
I’m just going to quote the I’m just going to quote the the plain language the plain english summary on this just to give us an idea of what they’re saying they’re saying we don’t know whether either mectin compared to placebo or usual treatment at 28 days after treatment leads to more or fewer deaths they’re saying they don’t know it worsens or improves patient condition assessed by need for oxygen or ventilation they’re saying they don’t know increases or reduces unwanted events they’re saying they don’t know
0:19:30 | prevented covered 19 and they’re saying they
don’t know so that there’s a definite don’t know on that one just from the plain language summary there whereas the other two are positive so there we go let’s leave you to think about that for a little while that’s my best interpretation of the data as we have it now if i’ve got something wrong I will come back and correct it but it’s an ongoing situation
0:20:00 | and we really need our leaders to
be more definitive in the guidelines that they are currently giving thank you for watching let’s have a quick update from wefaffin now on I think the first one is ben we’ll maybe look at an update from ben so let’s look let’s look at ben now as well this is the community outreach project of course we are following in africa in uganda
0:20:30 | hello guys welcome to our channel this
is welfare andrew and we are back the community I am with my friend ben here now today is a special day and I’m so excited this is because at least now we have been able to come back in time
0:21:00 | ben still has some medicine we found
that he still has some of the food and the mother has told us that the appetite of dane has now improved now I believe this is because his pain is under control today we brought him some more food and some medicine to keep him for about two weeks again now today we are not only going to visit pain but we are also going to see
0:21:30 | hezekiah in the same video for those
of you have been following our videos something like two months ago we visited hezekiah who is a seven year old boy who has debates made us type one and we were able to teach the mother about the diabetic diet we bought for them some food and we also bought them a glucometer as I told I have been receiving reports that the hezekiah’s condition is now good they
0:22:00 | can be able to monitor his bloody
sugar and they have now knowledge on nutrition so today we are here you are going to see two videos in one we are going to visit hezekiah and we are going to work on ben as well so I’m going to start by cleaning benny’s wounds and then of course we have already given them the food and from here we shall move to see ezekiel because they come from the
0:22:30 | same location so guys enjoy this video
and now friends here I was dressing ben is wound after cleaning are they wounds I know some people are not comfortable with seeing the past that’s why I didn’t show when I was cleaning the past but the good thing is that the pain has reduced and the past is also reducing compared
0:23:00 | to the previous days when I used
to clean benny’s wound that means the medicine is helping him very well and at least even the appetite is there because his pain is under control and we are feeding him on a balanced diet so I just want to thank you all who have supported ben up to this time and you who have supported all the work that we are doing on this channel
0:23:30 | so guys the surgeon looked at the
x-ray of the bones and you know they were severely affected so he advised that we put a pen on a balanced diet and we be doing wound dressing and we give him some medicine we observe him for something like two
0:24:00 | months and then we go back and
do the x-ray again and see if the surgery can be done to help penis condition so for now I’m just doing what they instructed me to do as we wait for that time to come we have so far made now one month of dressing putting ben on a balanced stead and also giving him some medicine for pain
0:24:30 | so friends for now I’m doing what
I was instructed to do we have moved a period of now about one month out of two and we need to continue doing these things for about two months before we go back to see the sergeant so we need more prayers we need more support such that we shall keep being in this good condition
0:25:00 | until the time we shall go back
to meet the sergeant otherwise thank you very much for the love thank you very much for the care I don’t know how I can appreciate you but I just want to say thank you and I really love you thank you for standing with us and may god bless you so guys we are now done with window dressing now they will not capture from outside because
0:25:30 | when I started working on ben it
was drizzling outside hope you are able to see us clearly we are here seated in demi’s room here his buildings so I’m now done with the dressing room we are now moving to another place where we are going to visit hezekiah who is a 17 years old boy suffering from the british maritals type one I received information that is doing well so let’s
0:26:00 | go there and find out how he
is doing hello guys welcome to our channel once again we are finally at the mama hezekiah’s place we’ve found hezekiah is in very good condition mama has kept him very well easy blood sugar is under control and he is receiving proper medication I
0:26:30 | am so grateful to you all who
supported hezekiah during that time when we needed support remember we were able to [Music] and today we just came to check on him so we just got some little food again but our major purpose of coming
0:27:00 | yes i’ve asked him to wait for
you guys so this is the mother let me just ask her how hezekiah is doing and maybe
0:27:30 | [Music] is very okay that since the
last time we came and told them about the debt and we brought the the glucometer hezekiah’s life has improved so thank you guys for all the support
0:28:00 | that you give to the care and
thank you for all the support that you’ve given us along the way we are doing a lot of things but we could not have been able to do all these things alone but because of your support we are able to move and see different people so thank you very much if it is your first time here please consider subscribing like and share this video with all
0:28:30 | okie doke brilliant I just find that
this project just immensely moving fantastic so just a couple of the pages there now just on the ethical side of this rapha does everything properly he gets he is working he does work for an ngo although this is in addition to that work he is registered as a as a medical officer with the government and he always gets permission from the local authorities to work in a
0:29:00 | particular area and he gets permission from
the local village eldership as well and of course all of the the participants in the videos have given their permission and they’ve all was not just they’ve given permission they’ve all been delighted that someone’s taking an interest in their condition so just a couple of patients we’re following from the traffic we will carry on doing so links to with this channel links to that video links to an opportunity to support wifi with with patreon even if
0:29:30 | it’s only for a month or two
that will be brilliant as he expands his educational and medical outreaches which of course is is about the most cost effective way you can spend money on healthcare really and there we go I can understand it’s drizzling there the weather here is terrible it’s just rained all the time let me just show you it’s like just like constant constant rain if I turn those lights off you might better see it then it’s just just rain for days
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