Comparative therapeutic efficacy of remdesivir and combination lopinavir, ritonavir, and interferon beta against MERS-CoV

By T. Sheahan, Amy C. Sims, S. Leist, A. Schäfer, John J. Won, Ariane J. Brown, S. Montgomery, A. Hogg, D. Babusis, M. Clarke and 9 more. Nature Communications, 2020

1,642 citations recorded by the source corpus.

Middle East respiratory syndrome coronavirus (MERS-CoV) is the causative agent of a severe respiratory disease associated with more than 2468 human infections and over 851 deaths in 27 countries since 2012. There are no approved treatments for MERS-CoV infection although a combination of lopinavir, ritonavir and interferon beta (LPV/RTV-IFNb) is currently being evaluated in humans in the Kingdom of Saudi Arabia. Here, we show that remdesivir (RDV) and IFNb have superior antiviral activity to LPV and RTV in vitro. In mice, both prophylactic and therapeutic RDV improve pulmonary function and reduce lung viral loads and severe lung pathology. In contrast, prophylactic LPV/RTV-IFNb slightly reduces viral loads without impacting other disease parameters. Therapeutic LPV/RTV-IFNb improves pulmonary function but does not reduce virus replication or severe lung pathology. Thus, we provide in vivo evidence of the potential for RDV to treat MERS-CoV infections. Remdesivir (RDV) is a broad-spectrum antiviral drug with activity against MERS coronavirus, but in vivo efficacy has not been evaluated. Here, the authors show that RDV has superior anti-MERS activity in vitro and in vivo compared to combination therapy with lopinavir, ritonavir and interferon beta and reduces severe lung pathology.

Subfields: Animal Science and Zoology, Infectious Diseases

View Paper: https://www.semanticscholar.org/paper/6c3e8d0fde7d37c97f68675d4d8012c9445be551

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Animal Science and Zoology

1. Yizhao Peng
2. Xiaowei Li
3. Manman Geng
4. L. Meng
5. Shemin Lu

In Infectious Diseases

1. Guangdi Li
2. Yizhao Peng
3. Xiaowei Li
4. Manman Geng
5. Hongzhou Lu
6. L. Meng
7. Shemin Lu
8. E. de Wit

Citations in the corpus

• Intensive care management of coronavirus disease 2019 (COVID-19): challenges and recommendations (2020, neutral): “98 Not efficacious for Ebola virus disease compared with other investigational therapies; 67 superior activity compared with lopinavirritonavir in mice with MERS-CoV; 68 effectively inhibited SARS-CoV-2, MERS-CoV, and SARS-CoV in vitro 69, 70 No peer-reviewed, published safety data available for SAR”
• A Review of SARS-CoV-2 and the Ongoing Clinical Trials (2020, background): “Comparison between Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV), Middle East Respiratory Syndrome Coronavirus (MERS-CoV), and SARS-CoV-2 Whereas several human coronaviruses that cause mild respiratory diseases, such as HCoV-229E, HCoV-OC43, HCoV-NL63, and HCoV-HKU1, were estimated to cir”
• Remdesivir: A Review of Its Discovery and Development Leading to Emergency Use Authorization for Treatment of COVID-19 (2020, background): “51, 53 These findings, along with the safety profile of remdesivir in the clinical trial assessment against EBOV, 54 support the evaluation of remdesivir as a potential therapeutic drug for repurposing against the SARS-CoV-2 pandemic.”
• Should we stimulate or suppress immune responses in COVID-19? Cytokine and anti-cytokine interventions (2020, positive): “In vitro, IFN-α and -β have very systematically demonstrated robust efficacy against coronaviruses, but proved disappointing when transposed to human diseases [95,96,100,103].”
• Potential interventions for novel coronavirus in China: A systematic review (2020, background): “Remdesivir (RDV), a nucleoside analog GS‐5734, had been reported to inhibit human and zoonotic coronavirus in vitro and to restrain severe acute respiratory syndrome coronavirus (SARS‐CoV) in vivo.104 Recently, the antiviral activity of RDV and IFN‐β was found to be superior to that of LPV/RTV‐IFN‐β”
• The SARS, MERS and novel coronavirus (COVID-19) epidemics, the newest and biggest global health threats: what lessons have we learned? (2020, background): “A broad-spectrum antiviral nucleotide prodrug named remdesivir presented potent efficacy for the treatment of MERS coronavirus and SARS coronavirus in preclinical studies.(15,16) There are several similarities between these viruses in their diagnosis and treatment.”
• Prophylactic and therapeutic remdesivir (GS-5734) treatment in the rhesus macaque model of MERS-CoV infection (2020, background): “Efficacy studies in mice showed that remdesivir had therapeutic efficacy against Severe Acute Respiratory Syndrome (SARS)-CoV and MERS-CoV in Ces1c mice, deficient in a secreted carboxylesterase responsible for poor pharmacokinetics profile of remdesivir in mice, when administered before the peak of”