Prophylactic and therapeutic remdesivir (GS-5734) treatment in the rhesus macaque model of MERS-CoV infection

Proceedings of the National Academy of Sciences of the United States of America

Volumn 117, Issue 12, 2020, Pages 6771-6776

  de Wit, Emmie ^a   Feldmann, Friederike ^a   Cronin, Jacqueline ^a   Jordan, Robert ^b   Okumura, Atsushi ^c   Thomas, Tina ^a   Scott, Dana ^a   Cihlar, Tomas ^b   Feldmann, Heinz ^a  

^a NATIONAL INSTITUTES OF HEALTH   (United States)

^b GILEAD SCIENCES   (United States)

^c Columbia University ^*  (United States)

Author keywords

Animal model; Antiviral; MERS CoV; Remdesivir; Therapy

Indexed keywords

REMDESIVIR; ADENOSINE PHOSPHATE; ALANINE; ANTIVIRUS AGENT;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CONTROLLED STUDY; DISEASE SEVERITY; DRUG EFFICACY; FEMALE; HISTOPATHOLOGY; INOCULATION; LUNG LESION; MALE; MIDDLE EAST RESPIRATORY SYNDROME; MIDDLE EAST RESPIRATORY SYNDROME CORONAVIRUS; NONHUMAN; PRIORITY JOURNAL; RHESUS MONKEY; SEVERE ACUTE RESPIRATORY SYNDROME CORONAVIRUS 2; VIRUS CELL INTERACTION; VIRUS LOAD; VIRUS REPLICATION; ANIMAL; BETACORONAVIRUS; CORONAVIRUS INFECTION; DISEASE MODEL; DRUG EFFECT; LUNG; PANDEMIC; PATHOLOGY; PHYSIOLOGY; POST EXPOSURE PROPHYLAXIS; VIROLOGY; VIRUS PNEUMONIA;

ADENOSINE MONOPHOSPHATE; ALANINE; ANIMALS; ANTIVIRAL AGENTS; BETACORONAVIRUS; CORONAVIRUS INFECTIONS; COVID-19; DISEASE MODELS, ANIMAL; LUNG; MACACA MULATTA; MALE; MIDDLE EAST RESPIRATORY SYNDROME CORONAVIRUS; PANDEMICS; PNEUMONIA, VIRAL; POST-EXPOSURE PROPHYLAXIS; SARS-COV-2; VIRAL LOAD; VIRUS REPLICATION;

EID: 85081590720     PISSN: 00278424     EISSN: 10916490     Source Type: Journal    
DOI: 10.1073/pnas.1922083117     Document Type: Article

References (29)

1. World Health Organization, Coronavirus infections. https://www.who.int/csr/don/archive/disease/coronavirus_infections/en/. Accessed 25 January 2020.
2. K. Modjarrad et al., A roadmap for MERS-CoV research and product development: Report from a World Health Organization consultation. Nat. Med. 22, 701-705 (2016).
3. B. Brende et al., CEPI-a new global R&D organisation for epidemic preparedness and response. Lancet 389, 233-235 (2017).
4. M. K. Lo et al., GS-5734 and its parent nucleoside analog inhibit Filo-, Pneumo-, and Paramyxoviruses. Sci. Rep. 7, 43395 (2017).
5. T. K. Warren et al., Therapeutic efficacy of the small molecule GS-5734 against Ebola virus in rhesus monkeys. Nature 531, 381-385 (2016).
6. M. K. Lo et al., Remdesivir (GS-5734) protects African green monkeys from Nipah virus challenge. Sci. Transl. Med. 11, eaau9242 (2019).
7. T. P. Sheahan et al., Broad-spectrum antiviral GS-5734 inhibits both epidemic and zoonotic coronaviruses. Sci. Transl. Med. 9, eaal3653 (2017).
8. T. P. Sheahan et al., Comparative therapeutic efficacy of remdesivir and combination lopinavir, ritonavir, and interferon beta against MERS-CoV. Nat. Commun. 11, 222 (2020).
9. M. L. Agostini et al., Coronavirus susceptibility to the antiviral remdesivir (GS-5734) is mediated by the viral polymerase and the proofreading exoribonuclease. MBio 9, e00221-18 (2018).
10. E. de Wit et al., Middle East respiratory syndrome coronavirus (MERS-CoV) causes transient lower respiratory tract infection in rhesus macaques. Proc. Natl. Acad. Sci. U.S.A. 110, 16598-16603 (2013).
11. D. S. Hui et al., Middle East respiratory syndrome coronavirus: Risk factors and determinants of primary, household, and nosocomial transmission. Lancet Infect. Dis. 18, e217-e227 (2018).
12. A. Assiri et al., Epidemiological, demographic, and clinical characteristics of 47 cases of Middle East respiratory syndrome coronavirus disease from Saudi Arabia: A descriptive study. Lancet Infect. Dis. 13, 752-761 (2013).
13. J. F. Chan et al., Treatment with lopinavir/ritonavir or interferon-β1b improves outcome of MERS-CoV infection in a nonhuman primate model of common marmoset. J. Infect. Dis. 212, 1904-1913 (2015).
14. Z. Chen et al., Human neutralizing monoclonal antibody inhibition of Middle East respiratory syndrome coronavirus replication in the common marmoset. J. Infect. Dis. 215, 1807-1815 (2017).
15. E. de Wit et al., Prophylactic and therapeutic efficacy of mAb treatment against MERS-CoV in common marmosets. Antiviral Res. 156, 64-71 (2018).
16. D. Falzarano et al., Treatment with interferon-α2b and ribavirin improves outcome in MERS-CoV-infected rhesus macaques. Nat. Med. 19, 1313-1317 (2013).
17. N. van Doremalen et al., Efficacy of antibody-based therapies against Middle East respiratory syndrome coronavirus (MERS-CoV) in common marmosets. Antiviral Res. 143, 30-37 (2017).
18. H. M. Al-Abdely et al., Middle East respiratory syndrome coronavirus infection dynamics and antibody responses among clinically diverse patients, Saudi Arabia. Emerg. Infect. Dis. 25, 753-766 (2019).
19. S. Y. Bin et al., Environmental contamination and viral shedding in MERS patients during MERS-CoV outbreak in South Korea. Clin. Infect. Dis. 62, 755-760 (2016).
20. J. Prescott et al., Pathogenicity and viral shedding of MERS-CoV in immunocompromised rhesus macaques. Front. Immunol. 9, 205 (2018).
21. J. Dörnemann et al., First newborn baby to receive experimental therapies survives Ebola virus disease. J. Infect. Dis. 215, 171-174 (2017).
22. M. Jacobs et al., Late Ebola virus relapse causing meningoencephalitis: A case report. Lancet 388, 498-503 (2016).
23. S. Mulangu et al.; PALM Writing Group; PALM Consortium Study Team, A randomized, controlled trial of Ebola virus disease therapeutics. N. Engl. J. Med. 381, 2293-2303 (2019).
24. ClinicalTrials.gov, GS-5734 to assess the antiviral activity, long-term clearance of Ebola virus and safety in male Ebola survivors with evidence of Ebola virus persistence in semen. https://clinicaltrials.gov/ct2/show/NCT02818582?term=NCT02818582&draw=2&rank=1. Accessed 25 January 2020.
25. ClinicalTrials.gov, Investigational therapeutics for the treatment of people with Ebola virus disease. https://clinicaltrials.gov/ct2/show/NCT03719586?term=remdesivir&rank=1. Accessed 25 January 2020.
26. World Health Organization, Novel coronavirus (2019-nCoV). https://www.who.int/emergencies/diseases/novel-coronavirus-2019. Accessed 25 January 2020.
27. D. Falzarano et al., Infection with MERS-CoV causes lethal pneumonia in the common marmoset. PLoS Pathog. 10, e1004250 (2014).
28. D. L. Brining et al., Thoracic radiography as a refinement methodology for the study of H1N1 influenza in cynomologus macaques (Macaca fascicularis). Comp. Med. 60, 389-395 (2010).
29. V. M. Corman et al., Detection of a novel human coronavirus by real-time reverse-transcription polymerase chain reaction. Euro. Surveill. 17 20285 (2012).