Antiparasitic Ivermectin as Antiviral for COVID-19
Ivermectin in Glycine Chloride Channels mechanisms of COVID-19.
Antiparasitic, one word that comes from people that doubting Ivermectin as drugs for COVID-19. For public, this statement seems to be true. Even WHO doesn't put Ivermectin on the stage. If we browse some medics channel at YouTube, still the pros and contras do exist.
Data from 'few' studies and researches show that Ivermectin can be used as antiviral for COVID-19. The mechanisms of Ivermectin in Spike (S), Membrane (M), Nucleocapsid (N), Papain-like protease (PLPro) as anti-inflammatory agent, as inhibitor of CD147-S protein binding, as ionophore agent (affecting the hydro-electrolyte balance) have been analized and shared1.
Ivermectin Works in Some Parts of India
In April-May 2021, India reported a significant rise of positive cases and deaths because of COVID-19, with majority infected by Delta variant (B.1.617.2). Ivermectin implementation in certain regions of India i.e. Uttar Pradesh, Delhi, Goa, Uttarkhand, Karnatarka have experienced dramatic decreases upon infections and death rates. These facts were put by COVID-19 Front Line Critical Care Alliance (FLCCC) Allliance in an official letter to Indonesia Minister of Health, pleaded the implementation of Ivermectin as treatment and prophylaxis for COVID-192.
A preprint paper in bioRxiv posted in June 23, 2021 reported that this variant evaded control by antibodies induced upon infection and BNT162b2 vaccination3. Delta variant also resistant against Bamlanivibab, an mAbs (monoclonal antibodies) for COVID-19. This variant has a higher transmissibility, more pathogenic and created a bigger Syncytia (multi-nucleated giant cells). The preprint also reported infections in colon though the researchers didn't detect increased ACE2-S protein binding of delta variant, suggested another receptor was used by this virus to bind our cells. The fusion was ~2.5 fold in human lung cell line, more efficient as compared to wild type of S protein.
Ivermectin as AntiParasite in Nematodes
The Ivermectin-sensitive channel on nematode is a glutamate-activated chloride channels, GluCls4. The antiparasitic pathway of Ivermectin is it's binding to glutamate-activated chloride channels, existing in nerve or muscle cells of nematode with a specific and high affinity, causing hyperpolarization of nerve or muscle cells by increasing permeability of chloride ion through the cell membrane, and as a result, the parasites are paralyzed to death. The channels are found only in protostome invertebrate phyla but are closely related to mammalian glycine receptors5. When Ivermectin binds to the GluCls, it potentiates the channel activity, resulting in hyperpolarization of parasite neurons and muscles, thereby killing the parasites.
Ivermectin, Glycine, and Chloride Channels for COVID-19
Ivermectin can act as a partial agonist for glycine-gated strychnine-inhibitable chloride channels. These channels have a number of types of immune cells—including alveolar macrophages and neutrophils—as well as vascular endothelium. The anti-inflammatory effects of high-dose dietary glycine in rodents have showed to activate of such channels on immune and endothelial cells6. In rats, high dietary glycine (5% of diet) has been shown to halve the mortality of a lethal dose of lipopolysaccharide (LPS). LPS in SARS-CoV-2 is located in the cleavage of S1/S2. Ivermectin 1 mM suppresses the activating effect of LPS on Kupffer cells in vitro. Removal of chloride from that medium completely eliminates Ivermectin’s impact in this regard.
Ivermectin could boost the activity of systemic glycine receptors in humans. The pathway that has been used as antiparasitic drugs, is used in COVID-19 through glycine-gated strychnine-inhibitable chloride channels. It is explainable the antiparasitic drugs can be used as antiviral and anti-inflammatory agent in COVID-19. Like a sword, Ivermectin is not only used for a spesific enemy.
https://www.nature.com/articles/s41429-021-00430-5#Tab2
https://t.co/eVWAQrCue7?amp=1
https://www.biorxiv.org/content/10.1101/2021.06.23.449568v1
https://pubmed.ncbi.nlm.nih.gov/14639007/
https://physoc.onlinelibrary.wiley.com/doi/full/10.1113/JP275236
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8057070/