A #drug #repurposing screen identifies #antiviral compounds against #Puumala #Orthohantavirus

Abstract

Hantaviruses are zoonotic negative-sense RNA viruses that cause haemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS), yet no approved antiviral therapies are available. To identify host-directed modulators of hantavirus infection we performed a drug repurposing screen using live Puumala virus (PUUV). We identified and validated 70 drugs with antiviral activity in A549 cells and primary human endothelial cells. Functional clustering confirmed the known infection-inhibitory effect of several groups of compounds, including inhibitors of heat shock proteins, mTOR pathway and nucleotide synthesis. Our screen also identified compounds yet unexplored as antivirals against Hantaviruses, such as certain antibiotics. Our dataset provides a systematic map of host pathways influencing PUUV infection and highlights candidate compounds and cellular processes that can modulate this process.

Source: 

Link: https://www.nature.com/articles/s41598-026-57843-1

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#Diagnostic and #clinical #challenges of #hantavirus-associated acute #kidney injury

 

Abstract

Introduction: 

Hantavirus infection is an uncommon zoonosis in Europe but remains an important cause of acute kidney injury, particularly in patients with environmental exposure to rodents. Renal involvement is the hallmark of the disease, although pulmonary manifestations may coexist and mimic immune-mediated pulmonary–renal syndromes, leading to diagnostic challenges in internal medicine.

Case description: 

A 46-year-old previously healthy man living in a rural area was admitted for acute febrile illness with asthenia and myalgia. Initial investigations revealed severe thrombocytopenia and acute kidney injury with proteinuria and microscopic haematuria. A computed tomography scan of the chest and abdomen showed bilateral pulmonary abnormalities, consistent with an acute pulmonary–renal syndrome. Extensive immunological and infectious investigations excluded autoimmune disease and alternative infectious causes. Hantavirus infection was confirmed by positive IgM and IgG serology, with molecular identification of Puumala virus. Renal biopsy demonstrated moderate acute tubular necrosis with minimal interstitial inflammation and preserved glomeruli. The patient was treated with supportive care only, resulting in rapid clinical improvement and complete recovery of renal function.

Conclusion: 

Hantavirus infection should be considered in patients presenting with acute pulmonary–renal syndrome, thrombocytopenia, and compatible epidemiological exposure. Early diagnosis allows appropriate supportive management, avoids unnecessary immunosuppressive therapy, and is associated with an excellent renal prognosis in Puumala virus infection.

Source: 

Link: https://www.ejcrim.com/index.php/EJCRIM/article/view/6159

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Identification and #genetic characterization of a distinct #genotype of #Puumala #orthohantavirus in #Hebei Province, #China

 

Abstract

Orthohantavirus infections pose a significant threat to human health, while numerous orthohantaviruses have been identified, suspected viral infections remain undiagnosed in the world, which highlights the need for further identification and characterization of viruses circulating in humans and host animals. In this study, viral metagenomics was utilized to investigate orthohantaviruses present in tissue samples collected from rodents trapped at the Bashang Grassland of Hebei Province, China. A total of 145 wild rodents belonging to six species were captured in the study area, and 725 tissue samples (lung, liver, kidney, spleen, gut) were collected in 2024. A Puumala orthohantavirus (PUUV), named Guyuan strain, was identified in Myodes rufocanus, with a positive rate of 0.69%. The complete genomic sequences of the L, M, and S segments were obtained and confirmed by Sanger sequencing. Phylogenetic analysis of these genomic sequences with those of other orthohantavirus species showed that the L, M, and S segments clustered with PUUV genomic sequences, while sharing a nucleotide sequence similarity of 81.2%, 80.2%, and 84.3% with previously characterized reference viral strains Kitahiyama128L, Tobetsu_04, and Baltic/205 Cg, respectively. Amino acid homology analysis demonstrated that the sequences exhibited the highest identity to PUUV Hokkaido strain at a level of 95.4%, 94.6%, and 97.0% respectively. Viral particles were observed in lung and kidney tissues using transmission electron microscopy, and viral protein antigen was detected in viral RNA-positive lung, liver, and kidney tissues through immunofluorescence assay with antibodies against the PUUV nucleocapsid protein, thereby confirming the virus’s multiorgan tropism. The results demonstrated that a distinct genotype of PUUV was circulating in rodents in the study areas, which may have implications for zoonotic transmission surveillance and public health management in Hebei Province.

Source: 

Link: https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0014250

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