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

Abstract 

This study evaluated the efficacy of several known antiviral drugs (ribavirin, penciclovir, nitazoxanide, nafamostat, chloroquine, remdesivir, and favipiravir) in treating 2019-nCoV. These medications were tested on lab isolated 2019-nCoV in vitro. A series of standard assays were used to gather cytotoxicity, virus yield, and infection rate data. Overall, remdesivir and chloroquine stand out for their effectiveness against 2019-nCoV and because of the experience the medical community has with them. 


Introduction 

This study suggests that the development of drugs fighting novel coronavirus can be expedited if existing antiviral medications are experimented with. The researchers selected several FDA approved antivirals, attempting to lay groundwork for future 2019-nCoV treatment. 


Methods

In Vero E6 cells (cultures good for propagating viruses)  were infected with Wuhan sourced nCoV and were used to test the medications. The first step in this study was to evaluate the cytotoxicity (toxic effect on cells) of all the candidates tested. This was done with a CCK-8 assay (a method using dye to determine the number of living cells). Next, the effectiveness of the drugs was determined by observing the quantity of viral copies in the cells used after 48 hours. This step used RT-PCR along with visual confirmation based on microscopy of nucleoprotein expression. The tests performed came together in selectivity indexes (SI): ratios comparing cytotoxicity to antiviral activity. 

Results

Three of seven medications (including ribavirin) required large concentrations of three nucleoside analogues (nucleic acid analogue and sugar) in order to effectively fight the viral infection. Nafamostat (used to fight MERS-CoV) inhibited 2019-nCoV. Nitazoxanide was also inhibitive at a low molecular concentration. 

Most notably, however, remdesivir and chloroquine “potently blocked” virus infection at low concentrations with high SI (good ratio of antiviral effect vs toxicity to cells). Remdesivir inhibited virus infection on human liver cancer cells, which are susceptible to the virus. Chloroquine’s tests on infected in Vero E6 cells showed it is also effective, both on entry and post entry stages of the infection. The study proves that both of these medications are “highly effective in the control of 2019-nCoV infection in vitro.”


 Discussion

Past studies using non-human primate models showed that a 10mg/kg dose of remdesivir resulted in lasting levels of its effective form in blood and it has proven extremely (100%) effective against Ebola virus.

 Chloroquine has been used for decades as an antimalarial and autoimmune disease drug. It blocks virus infection by altering the pH conditions necessary for a virus to attach to a cell. The drug spreads effectively throughout the whole body and has a potentially beneficial immune-modulating property. It has a low cost and is safe with known doses. 

Further testing is recommended for certain medications, as past studies have shown discrepancies between tests performed on Vero cells and other samples, such as mice.