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A study recently published in Cell Research and conducted by researchers at the Wuhan Institute of Virology, Wuhan, China, has found that remdesivir, a currently non-FDA approved investigational anti-viral drug and chloroquine are highly effective in the control of 2019-nCoV (COVID-19) infection in vitro.
Standard assays were carried out to measure the effects of several candidate compounds – among which are, ribavirin, penciclovir, nitazoxanide, nafamostat, chloroquine and two broad-spectrum antiviral drugs remdesivir (GS-5734) and favipiravir (T-705) on the cytotoxicity, virus yield and infection rates of 2019-nCoVs in vitro.
The cytotoxicity of the candidate compounds in Vero E6 cells (ATCC-1586) was determined by the CCK8 assay. Then, Vero E6 cells were infected with nCoV-2019BetaCoV/Wuhan/WIV04/20192 at a multiplicity of infection (MOI) of 0.05 in the presence of varying concentrations of the test drugs.
DMSO was used in the controls.
Efficacies of the candidate compounds were evaluated by quantification of viral copy numbers in the cell supernatant via quantitative real-time RT-PCR (qRT-PCR) and confirmed with visualization of virus nucleoprotein (NP) expression through immunofluorescence microscopy at 48 h post infection (p.i.) (cytopathic effect was not obvious at this time point of infection).
Among the seven tested drugs, high concentrations of three nucleoside analogs including ribavirin (half-maximal effective concentration (EC50) = 109.50 μM, half-cytotoxic concentration (CC50) > 400 μM, selectivity index (SI) > 3.65),, penciclovir (EC50 = 95.96 μM, CC50 > 400 μM, SI > 4.17) and favipiravir (EC50 = 61.88 μM, CC50 > 400 μM, SI > 6.46) were required to reduce the viral infection.
The authors further reported that Nafamostat, a potent inhibitor of MERS-CoV, which prevents membrane fusion, was inhibitive against the 2019-nCoV infection (EC50 = 22.50 μM, CC50 > 100 μM, SI > 4.44). Nitazoxanide, a commercial antiprotozoal agent with an antiviral potential against a broad range of viruses including human and animal coronaviruses, inhibited the 2019-nCoV at a low-micromolar concentration (EC50 = 2.12 μM; CC50 > 35.53 μM; SI > 16.76).
Remdesivir, an adenosine analogue (EC50 = 0.77 μM; CC50 > 100 μM; SI > 129.87) and chloroquine, a widely-used anti-malarial and autoimmune disease drug, (EC50 = 1.13 μM; CC50 > 100 μM, SI > 88.50) potently blocked virus infection at low-micromolar concentration and showed high SI.
Study authors concluded saying: “Our findings reveal that remdesivir and chloroquine are highly effective in the control of 2019-nCoV infection in vitro. Since these compounds have been used in human patients with a safety track record and shown to be effective against various ailments, we suggest that they should be assessed in human patients suffering from the novel coronavirus disease.”
The in vitro experimental nature of the study is a significant limitation for its direct translation to human subjects. Well controlled multi-centre randomized clinical trials with large study population are needed in order to confirm the efficacies of the two drugs in treating COVID-19.
Wang, M., Cao, R., Zhang, L. et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res 30, 269–271 (2020). https://doi.org/10.1038/s41422-020-0282-0
Published: March 22, 2020
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