Can the experimental drug, remdesivir defeat 2019-nCoV?

On January 31, 2020, the New England Journal of Medicine reported the diagnosis, clinical course, and treatment of the first case of 2019 novel coronavirus in the United States. The good news is after treatment with intravenous remdesivir (a novel nucleotide analogue prodrug in development), the patient’s clinical condition improved. As of January 30, 2020, the patient remains hospitalized. He is afebrile, and all symptoms have resolved with the exception of his cough, which is decreasing in severity. However, the researchers write in the paper, although the use of remdesivir was based on the case patient’s worsening clinical status, the randomized controlled trials are needed to determine the safety and efficacy of remdesivir and any other investigational agents for treatment of patients with 2019-nCoV infection [1]. 

Remdesivir, the novel nucleotide analogue prodrug which has been used in the treatment is an experimental drug made by Gilead Sciences. As finding treatments to a new virus may take a long time, the scientists are trying to test the existing drugs to see whether they have activity against 2019-nCoV. Besides remdesivir, scientists are already trying antivirals used to treat HIV in hospitals to fight the new coronavirus. In the article published on January 24, 2020 in The Lancet, Chinese researchers said that “the combination of lopinavir and ritonavir was already available in the designated hospital, a randomized controlled trial has been initiated quickly to assess the efficacy and safety of combined use of lopinavir and ritonavir in patients hospitalised with 2019-nCoV infection.” [2] The treatment might work as to a study published in 2004 reported that the combination of these anti-HIV drug combination of lopinavir and ritonavir showed “substantial clinical benefit” when given to patients who had severe acute respiratory syndrome (SARS), a coronavirus similar to 2019-nCoV [3]. 

Similar study are also underway for the third coronavirus, Middle East respiratory syndrome coronavirus (MERS-CoV). Though there are no approved treatments for MERS-CoV infection, a combination of lopinavir, ritonavir and interferon beta (LPV/RTV-IFNb) is currently being evaluated in humans in Saudi Arabia. However, in a study published online in Nature Communications on 10 January shows that the combination of lopinavir, ritonavir and interferon beta only slightly reduces viral loads without impacting other disease parameters in MERS-infected mice [4]. The study was led by Dr. Ralph Baric of the University of North Carolina, Chapel Hill. In this study, researchers from Dr. Baric’s team show that in mice, both prophylactic and therapeutic remdesivir (RDV) improve pulmonary function and reduce lung viral loads and severe lung pathology. Thus, they provide in vivo evidence of the potential for RDV to treat MERS-CoV infections [4]. In an article published online on January 27 in Science, Mark Denison, a virologist at Vanderbilt University who has studied coronaviruses since 1984 says “Remdesivir has had activity against every coronavirus we’ve tested, and I’d be surprised if it didn’t have activity against this one (2019-nCoV).” Yuen Kwok-Yung, a microbiologist at the University of Hong Kong who co-authored a comprehensive analysis of potential coronavirus treatments in Nature Reviews Drug Discovery in 2016, also agrees that remdesivir is the most promising drug for 2019-nCoV and MERS [5].

On January 31, 2020, Gilead Sciences issued a statement from Merdad Parsey, MD, PhD, Chief Medical Officer on the company’s ongoing response to the 2019 novel coronavirus. According to the statement, “Gilead is working closely with global health authorities to respond to the novel coronavirus (2019-nCoV) outbreak through the appropriate experimental use of our investigational compound remdesivir.” And “Gilead is working with health authorities in China to establish a randomized, controlled trial to determine whether remdesivir can safely and effectively be used to treat 2019-nCoV.“[6]

The outbreak of 2019-nCoV has spread rapidly in China, and more cases are now confirmed in multiple countries. “While there are no antiviral data for remdesivir that show activity against 2019-nCoV at this time, available data in other coronaviruses give us hope.” As Merdad Parsey said in the statement. We look forward to seeing more data and study that the drugs do have good effects in the treatment for 2019-nCoV infection.

References

1. https://www.nejm.org/doi/full/10.1056/NEJMoa2001191

2. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30183-5/fulltext

3. Chu CM, Cheng VCC, Hung IFN, et al. Role of lopinavir/ritonavir in the treatment of SARS: initial virological and clinical findings. Thorax 2004;59:252-256.

4. Sheahan, T.P., Sims, A.C., Leist, S.R. et al. Comparativetherapeutic efficacy of remdesivir and combination lopinavir, ritonavir, andinterferon beta against MERS-CoV. Nat Commun 11, 222 (2020).

5. https://www.sciencemag.org/news/2020/01/can-anti-hiv-combination-or-other-existing-drugs-outwit-new-coronavirus

6. https://www.gilead.com/news-and-press/company-statements/gilead-sciences-statement-on-the-company-ongoing-response-to-the-2019-new-coronavirus