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)
By Xueting Yao, F. Ye, Miao Zhang, Cheng Cui, Baoying Huang, P. Niu, X. Liu, Li Zhao, Erdan Dong, Chunli Song and 5 more. Clinical Infectious Diseases, 2020
2,360 citations recorded by the source corpus.
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.
Subfields: Infectious Diseases, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/cdf2dad5fb4f43a967731749c6a4aece3ee68115
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Citations in the corpus
- The cytokine storm and COVID‐19 (2020, background): “vealed that low doses of HCQ might mitigate cytokine storm in patients with severe COVID‐19.(54) A small French trial showed significant reductions in viral load and the duration of viral infection for COVID‐19 patients who received 600 mg/day HCQ for 10 days,”
- The epidemiology, diagnosis and treatment of COVID-19 (2020, methodology): “Using physiologically-based pharmacokinetic (PBPK) models, hydroxychloroquine was found to be more potent than chloroquine in SARS-CoV-2-infected Vero cells [65] .”
- Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial (2020, background): “The target values indicated in this paper [14] were reached in our experiments.”
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- Effect of Hydroxychloroquine in Hospitalized Patients with COVID-19 (2020, background): “In-vitro studies suggest that high concentrations of hydroxychloroquine are required for maximal effects, although inhibitory concentrations derived from static Vero cell cultures are likely to provide, at best, an approximate guide to required in-vivo concentrations.(3) Hydroxychloroquine plasma co”
- The effect of control strategies to reduce social mixing on outcomes of the COVID-19 epidemic in Wuhan, China: a modelling study (2020, neutral): “Effective vaccines 42 and antivirals 43 that are being developed could counteract this global public health threat.”
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