Published On Oct 5, 2021
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Drugs Shown to Inhibit SARS-CoV-2 in COVID-19 Disease: Comparative Basic and Clinical Pharmacology of Molnupiravir and Ivermectin
https://austinpublishinggroup.com/pha...
/ leslie-adesuyi-ajayi-md-phd-fbpharmacols-f...
There are still many nations where vaccines are not yet widely available,
There is a gradual shift in focus, to antiviral drugs,
Adjunctive chemoprophylaxis
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...
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.
Cost
https://www.who.int/selection_medicin...
The cost for a package of 100 tablets of 3 mg ivermectin is $2.96.
Say, 12mg per day for 5 days = $0.53
Safety
http://www.vigiaccess.org
https://www.who-umc.org/vigibase/vigi...
Efficacy
Ivermectin
https://pubmed.ncbi.nlm.nih.gov/34145...
For deaths, average risk ratio 0.38, (62% benefit) (moderate-certainty evidence
https://ivmmeta.com
Early treatment
Late treatment
Prophylaxis
https://www.cochranelibrary.com/cdsr/...
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
Preventing COVID-19
We don't know whether ivermectin leads to more or fewer deaths compared with no drug