SassyLady
09-07-2021, 10:04 AM
That Ivermectin would work against Covid
https://www.sciencedirect.com/science/article/pii/S0166354220302011
Fig. 1. Ivermectin is a potent inhibitor of the SARS-CoV-2 clinical isolate Australia/VIC01/2020. Vero/hSLAM cells were in infected with SARS-CoV-2 clinical isolate Australia/VIC01/2020 (MOI = 0.1) for 2 h prior to addition of vehicle (DMSO) or Ivermectin at the indicated concentrations. Samples were taken at 0–3 days post infection for quantitation of viral load using real-time PCR of cell associated virus (A) or supernatant (B). IC50 values were determined in subsequent experiments at 48 h post infection using the indicated concentrations of Ivermectin (treated at 2 h post infection as per A/B). Triplicate real-time PCR analysis was performed on cell associated virus (C/E) or supernatant (D/F) using probes against either the SARS-CoV-2 E (C/D) or RdRp (E/F) genes. Results represent mean ± SD (n = 3). 3 parameter dose response curves were fitted using GraphPad prism to determine IC50 values (indicated). G. Schematic of ivermectin's proposed antiviral action on coronavirus. IMPα/β1 binds to the coronavirus cargo protein in the cytoplasm (top) and translocates it through the nuclear pore complex (NPC) into the nucleus where the complex falls apart and the viral cargo can reduce the host cell's antiviral response, leading to enhanced infection. Ivermectin binds to and destabilises the Impα/β1 heterodimer thereby preventing Impα/β1 from binding to the viral protein (bottom) and preventing it from entering the nucleus. This likely results in reduced inhibition of the antiviral responses, leading to a normal, more efficient antiviral response.
The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro
Leon Caly (https://pubmed.ncbi.nlm.nih.gov/?term=Caly+L&cauthor_id=32251768) 1 (https://pubmed.ncbi.nlm.nih.gov/32251768/#affiliation-1), Julian D Druce (https://pubmed.ncbi.nlm.nih.gov/?term=Druce+JD&cauthor_id=32251768) 1 (https://pubmed.ncbi.nlm.nih.gov/32251768/#affiliation-1), Mike G Catton (https://pubmed.ncbi.nlm.nih.gov/?term=Catton+MG&cauthor_id=32251768) 1 (https://pubmed.ncbi.nlm.nih.gov/32251768/#affiliation-1), David A Jans (https://pubmed.ncbi.nlm.nih.gov/?term=Jans+DA&cauthor_id=32251768) 2 (https://pubmed.ncbi.nlm.nih.gov/32251768/#affiliation-2), Kylie M Wagstaff (https://pubmed.ncbi.nlm.nih.gov/?term=Wagstaff+KM&cauthor_id=32251768) 3 (https://pubmed.ncbi.nlm.nih.gov/32251768/#affiliation-3)
Affiliations expand
PMID: 32251768
PMCID: PMC7129059 (http://www.ncbi.nlm.nih.gov/pmc/articles/pmc7129059/)
DOI: 10.1016/j.antiviral.2020.104787 (https://doi.org/10.1016/j.antiviral.2020.104787)
Free PMC article
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Abstract
Although several clinical trials are now underway to test possible therapies, the worldwide response to the COVID-19 outbreak has been largely limited to monitoring/containment. We report here that Ivermectin, an FDA-approved anti-parasitic previously shown to have broad-spectrum anti-viral activity in vitro, is an inhibitor of the causative virus (SARS-CoV-2), with a single addition to Vero-hSLAM cells 2 h post infection with SARS-CoV-2 able to effect ~5000-fold reduction in viral RNA at 48 h. Ivermectin therefore warrants further investigation for possible benefits in humans.
Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.
https://www.sciencedirect.com/science/article/pii/S0166354220302011
Fig. 1. Ivermectin is a potent inhibitor of the SARS-CoV-2 clinical isolate Australia/VIC01/2020. Vero/hSLAM cells were in infected with SARS-CoV-2 clinical isolate Australia/VIC01/2020 (MOI = 0.1) for 2 h prior to addition of vehicle (DMSO) or Ivermectin at the indicated concentrations. Samples were taken at 0–3 days post infection for quantitation of viral load using real-time PCR of cell associated virus (A) or supernatant (B). IC50 values were determined in subsequent experiments at 48 h post infection using the indicated concentrations of Ivermectin (treated at 2 h post infection as per A/B). Triplicate real-time PCR analysis was performed on cell associated virus (C/E) or supernatant (D/F) using probes against either the SARS-CoV-2 E (C/D) or RdRp (E/F) genes. Results represent mean ± SD (n = 3). 3 parameter dose response curves were fitted using GraphPad prism to determine IC50 values (indicated). G. Schematic of ivermectin's proposed antiviral action on coronavirus. IMPα/β1 binds to the coronavirus cargo protein in the cytoplasm (top) and translocates it through the nuclear pore complex (NPC) into the nucleus where the complex falls apart and the viral cargo can reduce the host cell's antiviral response, leading to enhanced infection. Ivermectin binds to and destabilises the Impα/β1 heterodimer thereby preventing Impα/β1 from binding to the viral protein (bottom) and preventing it from entering the nucleus. This likely results in reduced inhibition of the antiviral responses, leading to a normal, more efficient antiviral response.
The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro
Leon Caly (https://pubmed.ncbi.nlm.nih.gov/?term=Caly+L&cauthor_id=32251768) 1 (https://pubmed.ncbi.nlm.nih.gov/32251768/#affiliation-1), Julian D Druce (https://pubmed.ncbi.nlm.nih.gov/?term=Druce+JD&cauthor_id=32251768) 1 (https://pubmed.ncbi.nlm.nih.gov/32251768/#affiliation-1), Mike G Catton (https://pubmed.ncbi.nlm.nih.gov/?term=Catton+MG&cauthor_id=32251768) 1 (https://pubmed.ncbi.nlm.nih.gov/32251768/#affiliation-1), David A Jans (https://pubmed.ncbi.nlm.nih.gov/?term=Jans+DA&cauthor_id=32251768) 2 (https://pubmed.ncbi.nlm.nih.gov/32251768/#affiliation-2), Kylie M Wagstaff (https://pubmed.ncbi.nlm.nih.gov/?term=Wagstaff+KM&cauthor_id=32251768) 3 (https://pubmed.ncbi.nlm.nih.gov/32251768/#affiliation-3)
Affiliations expand
PMID: 32251768
PMCID: PMC7129059 (http://www.ncbi.nlm.nih.gov/pmc/articles/pmc7129059/)
DOI: 10.1016/j.antiviral.2020.104787 (https://doi.org/10.1016/j.antiviral.2020.104787)
Free PMC article
Full text linksCite
Abstract
Although several clinical trials are now underway to test possible therapies, the worldwide response to the COVID-19 outbreak has been largely limited to monitoring/containment. We report here that Ivermectin, an FDA-approved anti-parasitic previously shown to have broad-spectrum anti-viral activity in vitro, is an inhibitor of the causative virus (SARS-CoV-2), with a single addition to Vero-hSLAM cells 2 h post infection with SARS-CoV-2 able to effect ~5000-fold reduction in viral RNA at 48 h. Ivermectin therefore warrants further investigation for possible benefits in humans.
Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.