Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro | Cell Research

https://www.nature.com/articles/s41422-020-0282-0

Remdesivir has been recently recognized as a promising antiviral drug
against a wide array of RNA viruses (including SARS/MERS-CoV5) infection in cultured cells, mice and nonhuman primate (NHP) models. It is currently under clinical development for the treatment of Ebola virus infection.6 Remdesivir is an adenosine analogue, which incorporates into nascent viral RNA chains and results in pre-mature termination.7 Our time-of-addition assay showed remdesivir functioned at a stage post virus entry (Fig. 1c, d),
which is in agreement with its putative anti-viral mechanism as a nucleotide analogue. Warren et al. showed that in NHP model, intravenous administration of 10 mg/kg dose of remdesivir resulted in concomitant persistent levels of its active form in the blood (10 μM) and conferred
100% protection against Ebola virus infection.7 Our data showed that EC90
value of remdesivir against 2019-nCoV in Vero E6 cells was 1.76 μM, suggesting its working concentration is likely to be achieved in NHP.
Our preliminary data (Supplementary information, Fig. S2) showed that remdesivir also inhibited virus infection efficiently in a
human cell line (human liver cancer Huh-7 cells), which is sensitive to 2019-nCoV.2

Chloroquine,
a widely-used anti-malarial and autoimmune disease drug, has recently been reported as a potential broad-spectrum antiviral drug.8,9 Chloroquine is known to block virus infection by increasing endosomal pH required for virus/cell fusion, as well as interfering with the
glycosylation of cellular receptors of SARS-CoV.10
Our time-of-addition assay demonstrated that chloroquine functioned at
both entry, and at post-entry stages of the 2019-nCoV infection in Vero E6 cells (Fig. 1c, d). Besides its antiviral activity, chloroquine has an immune-modulating activity, which may synergistically enhance its antiviral effect in vivo. Chloroquine is widely distributed in the whole body, including lung, after oral administration. The EC90 value of chloroquine against the 2019-nCoV in Vero E6 cells was 6.90 μM, which can be clinically achievable as demonstrated in the plasma of rheumatoid
arthritis patients who received 500 mg administration.11
Chloroquine is a cheap and a safe drug that has been used for more than 70 years and, therefore, it is potentially clinically applicable against the 2019-nCoV.

Our findings reveal that remdesivir and chloroquine are highly effective in the control of 2019-nCoV infection in vitro.

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