Hydroxychloroquine: Pharmacokinetics and Toxicity

Table 7

In vitro susceptibility to hydroxychloroquine of SARS-CoV-2 grown in African green monkey kidney Vero E6 cells.

Ref.	SARS-CoV-2 strain tested	HCQ concentrations tested, time of treatment administration, MOI^§	Antiviral effect evaluation method	Results	EC50 and EC90 converted from μM to μg/ml
[79]	IHUMI-3	0.1–100 μM, 4 h before viral infection, MOI = 0.25	Inhibition of viral replication (RT-PCR quantification) 48 h p.i.	EC50 = 1.5 ± 0.3 μM; EC90^£ = 3.0 ± 1.9 μM	EC50 = 0.65 ± 0.13; EC90 = 1.29 ± 0.82
[18]	IHUMI-3	HCQ 5 μM + azithromycin 5 μM or 10 μM, 4 h before viral infection, MOI = 0.25	Inhibition of viral replication (RT-PCR quantification) 60 h p.i.	97.5% and 99.1% viral inhibition, respectively
[80]	hCoV-19/Italy/UniSR1/2020	0.1–10 μM, 1 h before viral infection	Inhibition of virus CEP, 72 h p.i.; Inhibition of viral replication (RT-PCR quantification), 72 h p.i.	EC50^£ = 4.42 μM; EC50 = 4.99 μM	EC50 = 1.9; EC50 = 2.15
[81]	BetaCoV/Korea/SNU01/2020	1 or 2 μg/ml, 1 h p.i., MOI = 0.05	Inhibition of viral replication (RT-PCR quantification), 24 h and 48 p.i.	No effect compared to growth control
[58]	C Tan nCoV Wuhan strain 01	0.032–100 µM, 2 h p.i., MOI = 0.01	Inhibition of viral replication (RT-PCR quantification), 24 h and 48 h p.i.	EC50 = 6.14 µM and 0.72 μM, at 24 h and 48 h exposure	EC50 = 2.64 and 0.31 at 24 h and 48 h
[82]	Human strain isolated at Universitas Airlangga Hospital, Surabaya, Indonesia	0.2–400 μg/mL, 48 h p.i., MOI = 0.04	Inhibition of viral replication (RT-PCR quantification), 24 h, 48 h and 72 h p.i.	EC50 = 9.5 µg/ml, 4.7 µg/ml, and 1.4 µg/ml at 24 h, 48 h, and 72 h p.i. No viral production at 37.5 µg/ml
[83]	Provided by Egyptian Army	1.1 ± 0.13 µg/ml, 2 h p.i., MOI = 0.1	Inhibition of viral replication (RT-PCR quantification), 72 h p.i.	EC50 = 0.385 ± 0.01 µg/ml
[84]	MT121215.1	2–5 µM of RAC-HCQ (same as HCQ), R-HCQ or S-HCQ sulphate^&, 1 h before infection	Inhibition of viral replication (RT-PCR quantification), 48 h p.i.	EC50 = 5.09, 3.05, and 5.38 µM, for RAC-HCQ, R-HCQ, and S-HCQ sulphate, respectively	EC50 = 2.19, 1.31 and 2.31
[85]	USA-WA1/2020	1–50 µM, 1 h before infection	Inhibition of viral CPE, 48 h p.i.; Inhibition of viral RNA transcription (RT-PCR quantification), 48 h p.i.; Inhibition of production of infectious progeny viruses (TCID method^#), 48 h p.i.	EC50 = 16.5 µM; EC90 = 23 µM; EC50 = 18.6 µM; EC90 = 25.1 µM; EC50 = 21.7 µM; EC90 = 24.3 µM	EC50 = 7.09; EC90 = 9.89; EC50 = 7.99; EC90 = 10.8; EC50 = 9.33; EC90 = 10.45

p.i.: post-infection; PFU: plaque forming units; CEP: cytopathic effect. ^§MOI: multiplicity of infection, which represents the ratio of the number of virus particles to the number of the host cells at the time of cell infection. ^£EC50 and EC90: drug concentration allowing 50% and 90% of the assessed effect, respectively (e.g., inhibition of viral cytopathic effect or reduction in viral load). ^&Rac-HCQ, racemic hydroxychloroquine; R-HCQ, right-handed enantiomer of HCQ; S-HCQ, left-handed enantiomer of HCQ. ^#TCID50 or TCID90: amount of virus dilution required to induce cytopathic effects in 50% or 90% of wells containing the inoculated cell culture after a defined period.