A Twisting Tale of Misinformation: Should Ivermectin be Approved as a Treatment for COVID-19 Disease?

Shafiee, Arman; Athar, Mohammad Mobin Teymouri; Mozhgani, Sayed‐Hamidreza

doi:10.2217/fvl-2023-0006

Cited by 4 publications

(2 citation statements)

References 20 publications

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“…A literature screening reveals only few investigations that examine in vivo effects of ivermectin on schistosomes. The conclusions are mostly analogous to those relating to the applicability of ivermectin for COVID-19 therapy (Shafiee et al 2023 ): in both cases, there were in vitro significant results versus in vivo lack of success. Likewise, despite the pronounced effect on worm motility, there was no reduction of worm burden in infected mice following gavage treatment of 25 mg/kg ivermectin in 2 days, starting 6 weeks postinfection (Ryan et al 2023 ).…”

Section: Resultssupporting

confidence: 74%

Considering ivermectin for treatment of schistosomiasis

Golenser,

Birman,

Gold

2024

Parasitol Res

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Because of recent reports of praziquantel resistance in schistosome infections, there have been suggestions to employ ivermectin as a possible alternative, especially as its chemical composition is different from that of praziquantel, so cross-resistance is not expected. In order to ascertain possible damage and elimination of worms, we used ivermectin by oral gavage in infected mice, at a high dose (30.1 mg/kg, bordering toxicity). We also tested the efficacy of the drug at various times postinfection (PI), to check on possible effect on young and mature stages of the parasites. Thus, we treated mice on days 21 and 22 or on days 41 and 42 and even on days 21, 22, 41, and 42 PI. None of the treatment regimens resulted in cure rates or signs of lessened pathology in the mice. We also compared the effect of ivermectin to that of artemisone, an artemisinin derivative which had served us in the past as an effective anti-schistosome drug, and there was a stark difference in the artemisone’s efficacy compared to that of ivermectin; while ivermectin was not effective, artemisone eliminated most of the worms, prevented egg production and granulomatous inflammatory response. We assume that the reported lack of activity of ivermectin, in comparison with praziquantel and artemisinins, originates from the difference in their mode of action. In wake of our results, we suggest that ivermectin is not a suitable drug for treatment of schistosomiasis.

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Section: Resultssupporting

confidence: 74%

Considering ivermectin for treatment of schistosomiasis

Golenser,

Birman,

Gold

2024

Parasitol Res

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“…Multiple drug–protein interactions with viral and host proteins at the cell surface and cytoplasm interfere with virus entry and propagation and provide anti-inflammatory activities targeting JAK/signal transducer and activator of transcription (STAT), phosphatidylinositol-3 kinase/protein kinase B (PI3K/Akt), and nuclear factor kappa-light-chain enhancer of activated B cells (NF-kB) signaling pathways. However, evidence of its therapeutic benefits to treat COVID-19 is still lacking ( Shafiee et al, 2023 ).…”

Section: Introductionmentioning

confidence: 99%

Cholesterol and COVID-19—therapeutic opportunities at the host/virus interface during cell entry

Grewal,

Nguyen,

Buechler

2024

Life Sci. Alliance

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The rapid development of vaccines to combat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections has been critical to reduce the severity of COVID-19. However, the continuous emergence of new SARS-CoV-2 subtypes highlights the need to develop additional approaches that oppose viral infections. Targeting host factors that support virus entry, replication, and propagation provide opportunities to lower SARS-CoV-2 infection rates and improve COVID-19 outcome. This includes cellular cholesterol, which is critical for viral spike proteins to capture the host machinery for SARS-CoV-2 cell entry. Once endocytosed, exit of SARS-CoV-2 from the late endosomal/lysosomal compartment occurs in a cholesterol-sensitive manner. In addition, effective release of new viral particles also requires cholesterol. Hence, cholesterol-lowering statins, proprotein convertase subtilisin/kexin type 9 antibodies, and ezetimibe have revealed potential to protect against COVID-19. In addition, pharmacological inhibition of cholesterol exiting late endosomes/lysosomes identified drug candidates, including antifungals, to block SARS-CoV-2 infection. This review describes the multiple roles of cholesterol at the cell surface and endolysosomes for SARS-CoV-2 entry and the potential of drugs targeting cholesterol homeostasis to reduce SARS-CoV-2 infectivity and COVID-19 disease severity.

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