Prophylactic and therapeutic remdesivir (GS-5734) treatment in the rhesus macaque model of MERS-CoV infection
By E. de Wit, F. Feldmann, Jacqueline Cronin, R. Jordan, A. Okumura, T. Thomas, D. Scott, T. Cihlář, H. Feldmann. Proceedings of the National Academy of Sciences of the United States of America, 2020
821 citations recorded by the source corpus.
Significance Middle East Respiratory Syndrome, caused by the MERS coronavirus (MERS-CoV), continues to cause severe respiratory disease with a high case fatality rate. To date, potential antiviral treatments for MERS-CoV have shown limited efficacy in animal studies. Here, we tested the efficacy of the broad-acting antiviral remdesivir in the rhesus macaque model of MERS-CoV infection. Remdesivir reduced the severity of disease, virus replication, and damage to the lungs when administered either before or after animals were infected with MERS-CoV. Our data show that remdesivir is a promising antiviral treatment against MERS that could be considered for implementation in clinical trials. It may also have utility for related coronaviruses such as the novel coronavirus 2019-nCoV emerging from Wuhan, China. The continued emergence of Middle East Respiratory Syndrome (MERS) cases with a high case fatality rate stresses the need for the availability of effective antiviral treatments. Remdesivir (GS-5734) effectively inhibited MERS coronavirus (MERS-CoV) replication in vitro, and showed efficacy against Severe Acute Respiratory Syndrome (SARS)-CoV in a mouse model. Here, we tested the efficacy of prophylactic and therapeutic remdesivir treatment in a nonhuman primate model of MERS-CoV infection, the rhesus macaque. Prophylactic remdesivir treatment initiated 24 h prior to inoculation completely prevented MERS-CoV−induced clinical disease, strongly inhibited MERS-CoV replication in respiratory tissues, and prevented the formation of lung lesions. Therapeutic remdesivir treatment initiated 12 h postinoculation also provided a clear clinical benefit, with a reduction in clinical signs, reduced virus replication in the lungs, and decreased presence and severity of lung lesions. The data presented here support testing of the efficacy of remdesivir treatment in the context of a MERS clinical trial. It may also be considered for a wider range of coronaviruses, including the currently emerging novel coronavirus 2019-nCoV.
Subfields: Infectious Diseases
View Paper: https://www.semanticscholar.org/paper/4cf0991021e848323d8b269204e00fd807e96222
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In Infectious Diseases
Citations in the corpus
- Immunology of COVID-19: Current State of the Science (2020, positive): “Remdesivir has been previously shown to be effective against MERS-CoV and SARS-CoV-1 infections in animal models (Sheahan et al., 2017; de Wit et al., 2020) .”
- Remdesivir for 5 or 10 Days in Patients with Severe Covid-19 (2020, neutral): “4: Hospitalized, requiring low-flow supplemental oxygen 19 (10) 14 (7)”
- The epidemiology, diagnosis and treatment of COVID-19 (2020, methodology): “In a rhesus macaque model of MERS-CoV infection, prophylactic remdesivir treatment was initiated 24 h prior to inoculation, and MERS-CoV did not induce clinical disease and did not replicate in respiratory tissues, thus preventing the formation of lung lesions [51] .”
- Molecular immune pathogenesis and diagnosis of COVID-19 (2020, positive): “Remdesivir, an adenosine analogue that can target the RNA-dependent RNA polymerase and block viral RNA synthesis, has been a promising antiviral drug against a wide array of RNA viruses (including SARS/MERS-CoV) infections in cultured cells [58], mice [59] and nonhuman primate models [60,61].”
- Coronavirus Diseases (COVID-19) Current Status and Future Perspectives: A Narrative Review (2020, methodology): “use of remdesivir through an investigational new drug application has been described in various studies [44,45].”
- Infectious Diseases Society of America Guidelines on the Treatment and Management of Patients with COVID-19 (2022, background): “The efficacy of prophylactic and therapeutic remdesivir was tested in a rhesus macaque model of MERS-CoV infection [61].”
- SARS-CoV-2 Vaccines: Status Report (2020, background): “Remdesivir works against coronaviruses closely related to SARS-CoV-2 in animal models, as well as against the related MERS-CoV, including in NHPs (Agostini et al., 2018; Brown et al., 2019; de Wit et al., 2020; Sheahan et al., 2017 Sheahan et al., , 2020 .”
- Zoonotic Diseases: Etiology, Impact, and Control (2020, background): “The human fatality rate from MERS is around 30–35% [141], while the disease is asymptomatic in infected dromedaries.”
- Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial (2020, methodology): “17, 19 Such findings argue for testing of remdesivir earlier in COVID-19.”
- Surviving Sepsis Campaign: Guidelines on the Management of Critically Ill Adults with Coronavirus Disease 2019 (COVID-19) (2020, background): “Furthermore, studies in animal models of MERS-CoV showed that it was more effective than control and superior to lopinavir/ritonavir combined with systemic IFN-β (197, 198) .”
- Coronavirus disease 2019 (COVID-19): current status and future perspectives (2020, background): “Remdesivir The nucleoside analogue remdesivir (GS-5734) was reported to nhibit SARS-CoV and MERS-CoV in vivo [84 , 85] .”
- Remdesivir, lopinavir, emetine, and homoharringtonine inhibit SARS-CoV-2 replication in vitro (2020, background): “In addition, remdesivir (GS-5734), a prodrug of adenosine analog with a broad-spectrum antiviral activity against filoviruses, paramyxoviruses, and coronaviruses (Brown et al., 2019; Sheahan et al., 2017; de Wit et al., 2020) , was recently confirmed to inhibit 2019-nCoV in vitro .”