[chloroquine is an old-line drug typically used against malaria]
[partial quote follows]
ASBMB Today Science Could an old malaria drug help fight the new coronavirus?
Could an old malaria drug
help fight the new coronavirus?
By John Arnst
February 06, 2020
Chloroquine might be getting new life as an antiviral treatment for the novel coronavirus that emerged in Wuhan, China in late 2019 and has infected some 25,000 people in more than 25 countries. For decades, the drug was a front-line treatment and prophylactic for malaria.
In a three-page paper published Tuesday in Cell Research, scientists at the Wuhan Institute of Virology’s State Key Laboratory of Virology write that both chloroquine and the antiviral remdesivir were, individually, “highly effective” at inhibiting replication of the novel coronavirus in cell culture. Their drug screen evaluated five other drugs that were not effective. The authors could not be reached for comment.
Though the paper is brief, John Lednicky, a professor at the University of Florida’s Emerging Pathogens Institute, found its results intriguing. “It’s interesting in that it really lacks a lot of details but, nevertheless, if you look at the data as presented, at least in vitro, it seems like chloroquine can be used as an early-stage drug,” he said. “It would be very good if these types of experiments were repeated by more laboratories to see whether the same results occur across the board.”
Chloroquine is a synthetic form of quinine, a compound found in the bark of cinchona trees native to Peru and used for centuries to treat malaria.
Chloroquine was an essential element of mass drug administration campaigns to combat malaria throughout the second half of the 20th century, and remains one of the World Health Organization’s essential medicines. However, after the malaria parasites Plasmodium falciparum and Plasmodium vivax began exhibiting resistance to the drug in the 1960s and 1980s, respectively, it was replaced by similar antimalarial compounds and combination therapies. Chloroquine is still widely used against the three other species of plasmodium and to treat autoimmune disorders and some cases of amebiasis, an intestinal infection caused by the amoeba Entamoeba histolytica.
Chloroquine’s antiviral properties were explored in the mid-1990s against HIV and in the following decade against severe acute respiratory syndrome, or SARS, which is closely related to the novel coronavirus. In 2004, researchers in Belgium found that chloroquine inhibited replication of SARS in cell culture. The following year, however, another team at Utah State University and the Chinese University of Hong Kong evaluated a gamut of compounds against SARS replication in mice infected with the virus, finding that chloroquine was only effective as an anti-inflammatory agent. They recommended that it could be used in combination with compounds that prevent replication. Nevertheless, in 2009, the Belgian group found that lethal infections of human coronavirus OC43, a relative of SARS, could be averted in newborn mice by administering chloroquine through the mother’s milk.
[end of partial quote]
Also:
Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro
Manli Wang, Ruiyuan Cao, Leike Zhang, Xinglou Yang, Jia Liu, Mingyue Xu, Zhengli Shi, Zhihong Hu, Wu Zhong & Gengfu Xiao
Cell Research (2020)Cite this article
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Dear Editor,
In December 2019, a novel pneumonia caused by a previously unknown pathogen emerged in Wuhan, a city of 11 million people in central China. The initial cases were linked to exposures in a seafood market in Wuhan.1 As of January 27, 2020, the Chinese authorities reported 2835 confirmed cases in mainland China, including 81 deaths. Additionally, 19 confirmed cases were identified in Hong Kong, Macao and Taiwan, and 39 imported cases were identified in Thailand, Japan, South Korea, United States, Vietnam, Singapore, Nepal, France, Australia and Canada. The pathogen was soon identified as a novel coronavirus (2019-nCoV), which is closely related to sever acute respiratory syndrome CoV (SARS-CoV).2 Currently, there is no specific treatment against the new virus. Therefore, identifying effective antiviral agents to combat the disease is urgently needed.
An efficient approach to drug discovery is to test whether the existing antiviral drugs are effective in treating related viral infections. The 2019-nCoV belongs to Betacoronavirus which also contains SARS-CoV and Middle East respiratory syndrome CoV (MERS-CoV). Several drugs, such as ribavirin, interferon, lopinavir-ritonavir, corticosteroids, have been used in patients with SARS or MERS, although the efficacy of some drugs remains controversial.3 In this study, we evaluated the antiviral efficiency of five FAD-approved drugs including ribavirin, penciclovir, nitazoxanide, nafamostat, chloroquine and two well-known broad-spectrum antiviral drugs remdesivir (GS-5734) and favipiravir (T-705) against a clinical isolate of 2019-nCoV in vitro.
Standard assays were carried out to measure the effects of these compounds on the cytotoxicity, virus yield and infection rates of 2019-nCoVs. Firstly, 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 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 (Fig. 1a and Supplementary information, Fig. S1). However, favipiravir has been shown to be 100% effective in protecting mice against Ebola virus challenge, although its EC50 value in Vero E6 cells was as high as 67 μM,4 suggesting further in vivo studies are recommended to evaluate this antiviral nucleoside. 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). Further in vivo evaluation of this drug against 2019-nCoV infection is recommended. Notably, two compounds remdesivir (EC50 = 0.77 μM; CC50 > 100 μM; SI > 129.87) and chloroquine (EC50 = 1.13 μM; CC50 > 100 μM, SI > 88.50) potently blocked virus infection at low-micromolar concentration and showed high SI (Fig. 1a, b).
