Posted on 03/13/2020 8:50:15 PM PDT by Triple
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).
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. 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.
When I heard about chloroquine my optimism index spiked. That’s plain old quinine, used to treat malaria back in the day, and we can make it by the ton.
Yup - and remdesivir is a designer anti-viral - Tailored for coronavirus.
I took those malaria pills last summer wonder how long they are protective
01:16 PM EDT, 03/13/2020 (MT Newswires) — Gilead Sciences’ (GILD) remdesivir is said to have a positive effect in American cruise passengers who were treated for COVID-19 in Japan, the Wall Street Journal reported on Friday, citing a doctor sent by the US government to Tokyo.
National Institutes of Health assistant surgeon general and lung specialist Richard Childs said that remdesivir was administered to the 14 Americans who contracted the new coronavirus on the Diamond Princess cruise ship.
According to Childs, the 14 passengers, who had an average age of 75 years old, were critically ill. “Many of them were probably going to die in a short amount of time, and two weeks later nobody has died and more than half of them have recovered. It’s just absolutely amazing,” he said, though adding that it will take a while to determine the drug’s impact.
Gilead and independent groups are currently testing remdesivir in the US and Asia, but there remain no available large-scale results.
BFLR
U.S. Army Medical Research and Development Command has signed an arrangement with Gilead Sciences to provide the company’s investigational coronavirus drug to U.S. troops confirmed to have the COVID-19 virus.
Gilead’s medication, remdesivir, was approved for clinical research in February by the Food and Drug Administration. The medication, which initially was developed by the Foster City, California-based company to treat Ebola, has had some demonstrated success targeting coronaviruses, including Middle East Respiratory Syndrome, or MERS, and Severe Acute Respiratory Syndrome, SARS.
The medicine, given intravenously, is currently being tested for safety and effectiveness in two separate clinical trials in China and one by the National Institute of Allergy and Infection Diseases. In the U.S. study, the first volunteer was an evacuee from the Diamond Princess cruise ship hospitalized with the illness at the University of Nebraska Medical Center in Omaha.
play_circle_filledAmerican evacuees from China board a bus after arriving by flight to Eppley Airfield in Omaha, Neb., on Friday. The evacuees are to be quarantined at Camp Ashland, a nearby Nebraska National Guard training base. While the number of cases of COVID19 remain at 13 in the U.S., the military is making sure it’s ready if an outbreak were to occur. (Nati Harnik/AP)
US military prepping for coronavirus pandemic
U.S. Northern Command is bracing for an outbreak of the new coronavirus on U.S. soil, if it should occur.
Patricia Kime
Under the agreement between Gilead and U.S. Army Medical Materiel Development Activity, remdesivir will be provided to the Defense Department at no cost.
“Together with our government and industry partners, we are progressing at almost revolutionary rates to deliver effective treatment and prevention products that will protect the citizens of the world and preserve the readiness and lethality of our service members,” Army Brig. Gen. Michael Talley, commanding general of USAMRDC and Fort Detrick, Maryland, said in a statement Tuesday.
Gilead Science Chief Medical Officer Dr. Merdad Parsey said last month the speed of remdesivir’s development “reflects the pressing need for treatment options and the shared commitment” of industry, government and health services “to respond to this public health threat with the highest urgency.”
From military times - #7
Both are prescription. But yes, a ray of hope.
this was written last December.....
Yup - December 2019
I put the right date on the article, no?
I think remdesivir is given intravenously.
Gin and Tonic?
Well, in that case abandon a ray of hope
Your optimism spiked? Imagine mine. Gin and tonics. (Made with tonic water, quinine water, known to have inhibited malaria in Brits in the colonial tropics)
Excellent news. Please post a link to your source.
They’re both bullcrap expensive and dangerous
Colloidal silver kills all viruses and is risk free !
Yes, and didn’t Gilead already give patent rights to China?
My impression is that Gilead owns the patent, but is currently giving the drug away for trials and compassionate use.
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