Ivermectin or Molnupiravir

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Drugs Shown to Inhibit SARS-CoV-2 in COVID-19 Disease: Comparative Basic and Clinical Pharmacology of Molnupiravir and Ivermectin

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

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

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

Efficacy

Ivermectin

For deaths, average risk ratio 0.38, (62% benefit) (moderate-certainty evidence

Early treatment

Late treatment

Prophylaxis

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