The virus entry #inhibitor ARN-75039 provides therapeutic #protection against #Lassa virus infection in guinea pigs

 

Abstract

Lassa virus (LASV), a member of the Arenaviridae family, causes Lassa fever. There are no vaccines available for prevention of Lassa fever, and the primary therapeutic for treatment (ribavirin) has questionable antiviral activity and no formal approval for use. Here, we evaluated ARN-75039, an orally bioavailable broad-spectrum mammarenavirus entry inhibitor, against LASV infection in outbred Hartley guinea pigs exposed to a guinea pig–adapted LASV. ARN-75039 was administered for 14 days either 3 or 7 days postexposure (dpe) to LASV. In the first two studies, once-daily dosing at 3 dpe provided protection against lethal infection. A third study with twice-daily dosing at 7 dpe also achieved protection. Both drug regimens offered 100% protection at the lowest tested doses of 3.75 mg/kg (once-daily administration) or 7.5 mg/kg (twice-daily administration). ARN-75039–treated animals exhibited minimal disease signs and undetectable viremia. These results suggest that ARN-75039, for which a phase 1 human clinical trial has now been completed, may offer robust protection against LASV infection.

Source: 

Link: https://www.science.org/doi/10.1126/scitranslmed.adx0938

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Toddler in western #Cambodia becomes 16th #H5N1 bird #flu virus victim in 2025 (Antara)

 

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Phnom Penh (ANTARA) - A 3-year-old girl from Kampong Speu Province, western Cambodia, has been confirmed to have contracted H5N1 bird flu, bringing the number of cases to 16 so far this year, the Cambodian Ministry of Health said in a statement on Thursday (16/10) evening local time.

Laboratory results from Cambodia's National Institute of Public Health on October 15 showed the girl tested positive for the H5N1 virus, the statement said.

The patient had symptoms of fever, diarrhea, cough, and abdominal pain, and is currently undergoing intensive care with a team of doctors, the statement added.

The girl is a resident of Chek Village, Basedth District.

Investigations found that chickens and ducks had contracted the disease and died at the girl's home and at her neighbor's about a week before she fell ill, the statement said.

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Source: Antara, https://www.antaranews.com/berita/5181569/balita-di-kamboja-barat-jadi-korban-flu-burung-ke-16-pada-2025

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#Lassa Virus #Infection of Primary #Human #Airway Epithelial Cells

Abstract

Lassa mammarenavirus (LASV), a member of the family Arenaviridae, is a highly pathogenic virus capable of causing severe systemic infections in humans. The primary host reservoir is the Natal multimammate mouse (Mastomys natalensis), with human infections typically occurring through mucosal exposure to virus-containing aerosols from rodent excretions. To better understand the molecular mechanisms underlying LASV replication in the respiratory tract, we utilized differentiated primary human airway epithelial cells (HAECs) grown under air–liquid interface conditions, closely mimicking the bronchial epithelium in vivo. Our findings demonstrate that HAECs are permissive to LASV infection and support productive virus replication. While LASV entry into polarized HAECs occurred through both apical and basolateral surfaces, progeny virus particles were predominantly released from the apical surface, consistent with an intrinsic apical localization of the envelope glycoprotein GP. This suggests that apical virus shedding from infected bronchial epithelia may facilitate LASV transmission via airway secretions. Notably, limited basolateral release at later stages of infection was associated with LASV-induced rearrangement of the actin cytoskeleton, resulting in compromised epithelial barrier integrity. Finally, we demonstrate that LASV-infected HAECs exhibited a pronounced type III interferon response. A detailed understanding of LASV replication and host epithelial responses in the respiratory tract could facilitate the development of targeted future therapeutics.

Source: Viruses, https://www.mdpi.com/1999-4915/17/5/592

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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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