Clinical trials of Gilead Sciences’ remdesivir have begun in Wuhan, China, the center of the novel coronavirus outbreak, a day after Chinese researchers recommended that the antiviral drug candidate remdesivir be assessed in humans as a potential treatment for 2019-nCoV.

China’s National Medical Products Administration has approved applications by the China-Japan Friendship Hospital and the Chinese Academy of Medical Sciences to conduct trials evaluating remdesivir.

Today, China’s state-owned Xinhua news agency reported that Friendship Hospital plans to study a total of 761 patients in two trials—one trial to assess 308 with mild or moderate infection, the other 453 severely infected patients—at Jinyintan Hospital in Wuhan, under Phase III studies that have been officially launched.

“We hope good results will be achieved in the trials,” said Sun Yanrong, deputy director of the science and technology ministry’s China Biotechnology Development Center, at a press conference held by the National Health Commission.

According to updated coronavirus figures reported today by the National Health Commission, 65 people died and 3,887 more people were confirmed to be infected on Tuesday. To date, 24,324 people have been confirmed as infected with 2019-nCoV, and 490 people have died—more than the 349 who died in the SARS outbreak of 2002–03—with 892 patients cured and discharged from hospitals.

Xi Jinping, President of China

China has launched numerous initiatives in recent days aimed at controlling the outbreak, with Xinhua reporting today that President Xi Jinping said “the infection prevention and control is at a critical moment and stressed the utmost importance of carrying out the work in a law-based, scientific and orderly manner,” during the third meeting of the Commission for Overall Law-based Governance of the Communist Party of China Central Committee, headed by Xi.

Xi also signaled that China may hold some officials accountable for the nation’s initial slow response to containing 2019-nCoV: “Xi spoke of the need to improve legislation related to epidemic prevention and control, strengthen the building of supporting institutions and improve punishment procedures,” Xinhua reported. He has previously characterized China’s initial response as marked by “shortcomings and deficiencies.”

Remdesivir, chloroquine “highly effective”

The trials were announced as having begun a day after the experimental drug and a marketed anti-malarial, chloroquine, showed promising preclinical results.

“Our findings reveal that remdesivir and chloroquine are highly effective in the control of 2019-nCoV infection in vitro,” the researchers reported in “Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro,” a study published as a letter to the editor of the Nature-owned journal Cell Research.

“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 researchers added.

The research team consisted of investigators from the Wuhan Institute of Virology, Chinese Academy of Sciences / National Center for Biosafety and the National Academy of Military Medical Research Institute of Emergency Medicine for Prevention and Control of Drugs.

The researchers published their recommendation Tuesday, the same day that China’s Ministry of Science and Technology first said it would launch human clinical trials of remdesivir after a batch of the drug arrived in the country, Xinhua reported.

In their study, the researchers assessed remdesivir and chloroquine and five other drugs against a clinical isolate of 2019-nCoV in vitro. The five were: ribavirin, penciclovir, nitazoxanide, nafamostat, and favipiravir (T-705 or Avigan).

“Notably, 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 [selectivity index],” the researchers reported.

A time-of-addition assay showed remdesivir to function at a stage post virus entry, which according to the scientists appeared to reflect its putative anti-viral mechanism as a nucleotide analogue.

“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,” the researchers added. “Our preliminary data 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.”

Pursuing remdesivir patent

Remdesivir proved sufficient effective, the institutions added in a statement issued by the Wuhan Institute of Virology, that they have applied for Chinese invention patents on January 21 “in accordance with international practice and from the perspective of protecting national interests (Resistance to new coronaviruses in 2019).”

The institutions stated that they also plan to pursue multiple patents worldwide as allowed under the global Patent Cooperation Treaty.

However, the institutions added that should Gilead “intend to contribute to China’s epidemic prevention and control, we both agree that if the state needs it, we will not require the implementation of the rights claimed by the patent for the time being.”

The institutions have opted not to pursue patents for chloroquine, which is already marketed in China, also with the aim of encouraging partners to join them in efforts to prevent and control the spread of coronavirus.

Gilead said on January 31 that it will partner with officials to carry out clinical trials of remdesivir, and has offered the Nuc inhibitor for use in a “small number” of patients with 2019-nCoV for emergency treatment in the absence of any approved treatment options. The company added that it is also expediting “appropriate” laboratory testing of remdesivir against 2019-nCoV samples.

Gilead chief medical officer Merdad Parsey, MD, PhD, has cited positive in vitro and in vivo activity shown by remdesivir in animal models against MERS and SARS, coronaviruses that are structurally similar to 2019-nCoV.

Remdesivir also showed “no adverse events” after it was administered as a treatment to the first American confirmed to be infected with 2019-nCoV, according to “First Case of 2019 Novel Coronavirus in the United States,” a case study published Friday in The New England Journal of Medicine by members of the Washington State 2019-nCoV Case Investigation Team.

Rating unchanged despite potential

“This case-report suggests that remdesivir could be an effective treatment for 2019-nCoV and should be formally investigated as a therapeutic agent for the treatment of 2019-nCoV pneumonia, and we are encouraged by Gilead’s efforts to further investigate remdesivir, through the recently initiated trial in collaboration with Chinese health authorities,” SVB Leerink director of therapeutics research and senior research analyst, Geoffrey C. Porges, MBBS, wrote Monday in an investor note along with colleagues Neil Puri, MD, Ke (Andrew) Yuan, CFA, CPA, and Bradley Canino, CPA.

They added, however, that they would not change SVB Leerink’s “Market Perform” rating of Gilead stock as a result of remdesivir’s potential in treating coronavirus.

“From a societal perspective, we are unequivocally supportive of Gilead’s (and other company’s) efforts to develop an effective treatment for this rapidly spreading, and potentially fatal, infection; however these activities do not alter our fundamental assessment and outlook for GILD’s stock, as therapies of this nature are likely to provide a short-term financial boost, but unlikely to yield a significant impact on long-term shareholder value,” Porges and colleagues wrote.

Atazanavir, an antiretroviral medication used to treat and prevent HIV, was the most promising chemical compound to emerge from an artificial intelligence-based prediction model for antiviral drugs that may be effective on 2019-nCoV, according to an article posted Sunday on the bioRxiv preprint server by researchers at Deargen and Dankook University in South Korea, and Emory University in Atlanta—the latest report in GEN’s ongoing coverage of the 2019-nCoV novel coronavirus outbreak.

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