Nüssing S, Mifsud E, Hensen L, et al. Viral Burden, Inflammatory Milieu and CD8 + T-cell Responses to Influenza Virus in a Second-Generation Thiazolide (RM-5061) and Oseltamivir Combination Therapy Study. Influenza Other Respir Viruses. 2020;10.1111/irv.1
Background: Influenza viruses cause significant morbidity and mortality, especially in young children, elderly, pregnant women and individuals with co-morbidities. Patients with severe influenza disease are typically treated with one neuraminidase inhibitor, oseltamivir or zanamivir. These antivirals need to be taken early to be most effective and often lead to the emergence of drug resistance and/or decreased drug susceptibility. Combining oseltamivir with another antiviral with an alternative mode of action has the potential to improve clinical effectiveness and reduce drug resistance.
Methods: In this study, we utilized a host-targeting molecule RM-5061, a second-generation thiazolide, in combination with oseltamivir to determine whether these compounds could reduce viral burden and understand their effects on the immune response to influenza virus infection in mice, compared with either monotherapy or placebo.
Results: The combination of RM-5061 and OST administered for 5 days after influenza infection reduced viral burden at day 5 post-infection, when compared to placebo and RM-5061 monotherapy, but was not significantly different from oseltamivir monotherapy. The inflammatory cytokine milieu was also reduced in animals which received a combination therapy when compared to RM-5061 and placebo-treated animals. Antiviral treatment in all groups led to a reduction in CD8+ T-cell responses in the BAL when compared to placebo.
Conclusions: To our knowledge, this is the first time a combination of a host-targeting compound, RM-5061, and neuraminidase inhibitor, OST, has been tested in vivo. This antiviral combination was safe in mice and led to reduced inflammatory responses following viral infection when compared to untreated animals.
Methods: In this study, we utilized a host-targeting molecule RM-5061, a second-generation thiazolide, in combination with oseltamivir to determine whether these compounds could reduce viral burden and understand their effects on the immune response to influenza virus infection in mice, compared with either monotherapy or placebo.
Results: The combination of RM-5061 and OST administered for 5 days after influenza infection reduced viral burden at day 5 post-infection, when compared to placebo and RM-5061 monotherapy, but was not significantly different from oseltamivir monotherapy. The inflammatory cytokine milieu was also reduced in animals which received a combination therapy when compared to RM-5061 and placebo-treated animals. Antiviral treatment in all groups led to a reduction in CD8+ T-cell responses in the BAL when compared to placebo.
Conclusions: To our knowledge, this is the first time a combination of a host-targeting compound, RM-5061, and neuraminidase inhibitor, OST, has been tested in vivo. This antiviral combination was safe in mice and led to reduced inflammatory responses following viral infection when compared to untreated animals.
See Also:
Latest articles in those days:
- mRNA vaccines encoding computationally optimized hemagglutinin elicit protective antibodies against future antigenically drifted H1N1 and H3N2 influenza viruses isolated between 2018-2020 9 hours ago
- Clinical Characteristics of 118 Pediatric Patients With Acute Benign Myositis Associated With Influenza A Virus Infection 9 hours ago
- Avian Influenza A Viruses Modulate the Cellular Cytoskeleton during Infection of Mammalian Hosts 9 hours ago
- Seroprevalence of Avian Influenza A(H5N6) Virus Infection, Guangdong Province, China, 2022 2 days ago
- Clinical Presentation, Risk Factors, and Comparison of Laboratory Diagnostics for Seasonal Influenza Virus Among Cambodians From 2007 to 2020 2 days ago
[Go Top] [Close Window]