Hydroxychloroquine beats remdesivir in drug fight against Covid-19!!
#91
09 March 2020

Hydroxychloroquine was found to be more potent than chloroquine to inhibit SARS-CoV-2 in vitro.

In Vitro Antiviral Activity and Projection of Optimized Dosing Design of Hydroxychloroquine for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)


Source: https://www.ncbi.nlm.nih.gov/pmc/article...iaa237.pdf

Quote: Abstract

Background: The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) first broke out in Wuhan (China) and subsequently spread worldwide. Chloroquine has been sporadically used in treating SARS-CoV-2 infection. Hydroxychloroquine shares the same mechanism of action as chloroquine, but its more tolerable safety profile makes it the preferred drug to treat malaria and autoimmune conditions. We propose that the immunomodulatory effect of hydroxychloroquine also may be useful in controlling the cytokine storm that occurs late-phase in critically ill SARS-CoV-2 infected patients. Currently, there is no evidence to support the use of hydroxychloroquine in SARS-CoV-2 infection.

Methods: The pharmacological activity of chloroquine and hydroxychloroquine was tested using SARS-CoV-2 infected Vero cells. Physiologically-based pharmacokinetic models (PBPK) were implemented for both drugs separately by integrating their in vitro data. Using the PBPK models, hydroxychloroquine concentrations in lung fluid were simulated under 5 different dosing regimens to explore the most effective regimen whilst considering the drug's safety profile.

Results: Hydroxychloroquine (EC50=0.72 μM) was found to be more potent than chloroquine (EC50=5.47 μM) in vitro. Based on PBPK models results, a loading dose of 400 mg twice daily of hydroxychloroquine sulfate given orally, followed by a maintenance dose of 200 mg given twice daily for 4 days is recommended for SARS-CoV-2 infection, as it reached three times the potency of chloroquine phosphate when given 500 mg twice daily 5 days in advance.

Conclusions: Hydroxychloroquine was found to be more potent than chloroquine to inhibit SARS-CoV-2 in vitro.

Surprised
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#92
hydroxy chloroquine seems to prevent infection.

Remdesivir expedite recovery.

Don't try to use it the other way around.
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#93
23-5-2020 10:25 AM
sudoku said:
hydroxy chloroquine seems to prevent infection.

Remdesivir expedite recovery.

Don't try to use it the other way around.

Hydroxychloroquine does both. Remdesivir can prevent?

Cool
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#94
23-5-2020 10:30 AM
FaTa said:
Hydroxychloroquine does both. Remdesivir can prevent?

Cool

Former have higher mortality rate in treatment. Trump using as prevention.

Latter expedite recovery.

Vaccine still to be approved.
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#95
Source: https://www.jstage.jst.go.jp/article/ddt...5/_article

Drug Discoveries & Therapeutics

Rapid Review for the Anti-Coronavirus Effect of Remdesivir

Published: April 30, 2020
Received: March 06, 2020
Released: May 06, 2020
Accepted: April 28, 2020
[Advance Publication] Released: -
Revised: April 28, 2020

Quote:3. SARS-CoV-2
Wang et al. conducted an experiment to evaluate the anti-SARS-CoV-2 effect of remdesivir (10). In time-of-addition assay using Vero E6 cells, remdesivir was found to be effective when administered 2 hours after infection at a multiplicity of infection (MOI) of 0.05. However, no prophylactic effect was observed when remdesivir was administered prior to the SARS-CoV-2 infection. The concentration for 90% of maximal effect (EC90) value of remdesivir against SARS-CoV-2 was found to be 1.76 μM. This study also revealed that remdesivir could inhibit SARS-CoV-2 infection in human liver cancer Huh-7 cells.The recent case report recorded.

The current evidence on experimental studies and clinical observation indicated that remdesivir has the potential for treating COVID-19. Nevertheless, findings from the compassionate-use study were not adequately powered with a randomized controlled design to assess the safety and efficacy of remdisivir in patients with severe COVID-19. Therefore, more evidence from randomized clinical trials (RCTs) of high quality is eventually needed to confirm its safety and efficacy.

Two phase III clinical trials had been launched in Hubei and Beijing in China in early February 2020, aiming to evaluate the safety and efficacy of remdesivir for adult patients with COVID-19 and with mild-moderate (NCT04252664, sample size: 308) and severe (NCT04257656, sample size: 452) symptoms. Subsequently, other five RCTs with similar objectives were further registered on clinicaltrials.gov. However, as of 28th April 2020, there has not been published results available in the literature. Therefore, it remains largely unknown currently regarding the benefit-harm profile of remdesivir for COVID-19.

In brief, remdesivir has been found to inhibit coronavirus and improve pulmonary functions prophylactically and therapeutically (in early stage of infection) based on evidence from both in vitro and in vivo experiments. However, evidence in patients with COVID-19 remained limited and sparse. The ongoing clinical trials will provide more high-quality evidence on the benefit-harm effect of remdesivir. Nevertheless, there are several issues of concern regarding their protocols. First, the inclusion/exclusion criteria and the outcome measurements do not include chest radiography that is one of the key elements for disease diagnosis and criteria for recovery according to Guidelines for the Diagnosis and Treatment of Novel Coronavirus (SARS-CoV-2) Infection by the National Health Commission (Trial Version 5) published by National Health and Health Commission of the people's Republic of China (13). Thus, it may incur selection and reporting bias to weaken the results. Secondly, based on the previous experiments on SARS-CoV, remdesivir was effective only when it was administered at the early stage of infection (before the initiation of the immunopathological phase of pneumonia) (8). By contrast, another study showed that remdesivir was found to be functional for SARS-CoV-2 when administered 2 hours after infection (10). These results indicated the benefit of remdesivir may heavily depend on the time of administration. No predefined plans of trial designs or statistical analyses are given in their protocols related to the optimum time of administration. Thirdly, the current evidence was insufficient to support the safety of remdesivir in humans. Even though some cytotoxicity tests suggested that remdesivir could be effective at a relatively low micromolar concentration compared with its cytotoxic concentration (8,9), the safety test in humans is still ongoing currently. Moreover, a previous randomized controlled trial reported that in patients with Ebola virus disease, the overall mortality was even higher in remdesivir group (53%) than the control group (a triple monoclonal antibody agent; 50%), although without significance (14). Therefore, extreme cautions and monitoring should be taken in the ongoing trials for COVID-19 given the safety of remdesivir remains largely unconfirmed and unknown.

To summarize, even though remdesivir was proposed as a promising option for treating COVID-19 based on laboratory experiments and reports from compassionate use, its safety and effect in humans requires high-quality evidence from well-designed and adequately-powered clinical trials for further clarification. Similar to the inconclusive effect on SARS-CoV and MERS-CoV, the impact of remdesivir on the SARS-CoV-2 outbreak should not be overestimated in the current clinical practice. Further explorations remain urgently needed to treat the COVID-19 and bring the SARS-CoV-2 under control.
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#96
Trump is not an idiot, fortunately or unfortunately, depends on whether you like him or not.
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#97
23-5-2020 10:35 AM
sudoku said:
Former have higher mortality rate in treatment. Trump using as prevention.

Latter expedite recovery.

Vaccine still to be approved.

[Image: uUeXr7B.jpg]

As far as I know, the baseline used in the study are severely ill patients which is flawed & not honest at all. It was designed to fail and discredit hydroxychloroquine.

Hydroxychloroquine's usefulness is not in the late stage but early stage of infection.
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#98
23-5-2020 10:25 AM
sudoku said:
hydroxy chloroquine seems to prevent infection.

Remdesivir expedite recovery.

Don't try to use it the other way around.

Unlike hydroxychloroquine (which can prevent and recover), remdesivir is not able to prevent according to this review.

https://www.jstage.jst.go.jp/article/ddt...5/_article
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