Antiviral activities of multiple #antivirals against highly pathogenic avian #influenza A #H5N1 in vitro and in mice

 

ABSTRACT

In 2024, a bovine H5N1 strain was first isolated from dairy cows in Texas and confirmed to transmit cross-species to humans. Therefore, research on treatments for human infection should be accelerated. In our study, the antiviral effects of baloxavir acid (BXA), oseltamivir carboxylate (OSC), EIDD-1931 (NHC), and ribavirin (RBV) against five H5N1 strains were evaluated in vitro. Cell viability and viral replication were measured to assess the antiviral effects. The results showed that the EC50 of BXA treatment was the lowest. The BXA/NHC and BXA/OSC combination treatments showed more potent inhibitory effects than each monotherapy. The 15 mg/kg baloxavir marboxil (BXM) / 125 mg/kg molnupiravir (MNP) and the 15 mg/kg BXM / 10 mg/kg oseltamivir phosphate (OSP) were tested in BALB/c mice. The mice were inoculated with 10 times the 50% mouse lethal dose (10 MLD50) of bovine H5N1 virus. Treatments began 1-day post-infection (1 dpi) and were administered orally twice daily for 5 or 7 days. Changes in body weight, clinical signs, and survival were monitored; lung and brain tissues were collected for virological, immunological, and histological analyses. Most mice died from severe neurological symptoms. Compared with the 5-day treatment, the 7-day treatment effectively inhibited viral replication and increased survival rates to 50% in BXM, BXM/MNP, and BXM/OSP treatments. Mice treated with BXM/MNP or BXM/OSP combination therapy showed lower viral yields in the lungs than those treated with BXM alone. The results provide a reference for human treatment, and extending the 7-day combination treatment should be considered.

Source: Emerging Microbes and Infections, https://www.tandfonline.com/journals/temi20

Link: https://www.tandfonline.com/doi/full/10.1080/22221751.2026.2645843

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Coadministration of #ribavirin and #arenaviral entry #inhibitor LHF-535 enhances antiviral benefit against authentic #Lassa virus

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Highlights

• A new strain of Lassa virus (LASV) was successfully isolated and characterized.

• The combination of ribavirin and LHF-535 has been demonstrated to exhibit synergistic effects in inhibiting LASV.

• The findings provide new directions for the development of antiviral drugs and vaccines for Lassa fever.

Dear Editor,

Lassa virus (LASV) is the causative agent of the acute viral hemorrhagic Lassa fever (LF), which is classified into Mammarenavirus within the Arenaviridae family, with a single-stranded, negative-sense, bi-segmented RNA genome. Due to its high pathogenicity and lethality, LASV is considered as a priority threat to public health, with an estimated cases of 300,000 infections and 5,000 deaths annually. LASV was first isolated and described as a clinical entity in 1969 in Lassa, Nigeria (Garry, 2023). LASV isolates of different geographic and host origins are highly diverse in genomic sequences and phylogenetically classified into up to seven lineages, with each lineage predominately localized in specific countries. Although the research on LF has been carried out for decades since the pathogen first characterized, there is no approved antiviral drugs or vaccines for clinical use against LASV to date (Grant et al., 2023). One possible reason that hindered the development of countermeasures is that the preclinical studies on authentic LASV are restricted in high bio-containment biosafety level 4 (BSL-4) facilities. In this letter, we describe isolation, and characterization of the LASV from the clinical samples. And we applied a coadministration assay of antiviral drugs for LASV by using a clinically isolated Mammarenavirus lassaense strain in the BSL-4 facility, aiming to investigate new therapeutic strategies for LASV infection.

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Source: Virologica Sinica, https://www.sciencedirect.com/science/article/pii/S1995820X25000380?via%3Dihub

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Improving #clinical #care of patients in #Nipah #outbreaks: moving beyond ‘compassionate use’

Summary

The 2024 Nipah outbreak in Kerala, India—its fifth in six years—and the recurring annual outbreaks in Bangladesh underscore the persistent threat posed by the Nipah virus (NiV) in the region. With a high mortality rate, human-to-human transmission potential, and the widespread presence of Pteropus bats, the natural reservoir, NiV remains a significant epidemic threat. Despite being a WHO priority pathogen, there has been no systematic effort to improve patient care for NiVD, leading to consistently poor outcomes. Current care relies on supportive measures and the ‘compassionate use’ of unapproved drugs like ribavirin and remdesivir. Drugs used ‘off-label’ during outbreaks can become the ‘standard of care’ without robust evidence of their safety or efficacy, complicating the testing of new therapies and perpetuating uncertainty about their true effectiveness. To improve NiVD care, we propose four key strategies: 1) Enhance early case detection, 2) optimize supportive care to improve outcomes and create a standard for future trials, 3) adopt a syndromic approach centered on encephalitis, and 4) explore innovative trial designs tailored to low case numbers as an alternative to ‘compassionate use’. By integrating these strategies, healthcare systems in NiV-endemic regions will be better equipped to manage both current and future outbreaks.

Source: Lancet Regional Health South-East Asia, https://www.thelancet.com/journals/lansea/article/PIIS2772-3682(24)00177-X/fulltext

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