A study published in the journal Scientific Reports on June 28, 2026, identified 70 validated host-directed therapies that suppressed Puumala virus (PUUV) infection in human lung and endothelial cells. The findings resulted from a high-throughput phenotypic drug screening of 5,256 compounds from the Drug Repurposing Hub library.

The research utilized live PUUV for the screening process. Initially, A549 human lung adenocarcinoma epithelial cells were used for the primary screening. Out of 5,256 molecules tested, 151 were identified as candidate antiviral drugs, reducing the infection rate by at least 2-fold compared to control groups.

Human umbilical vein endothelial cells (HUVECs) were used for validation. Subsequent validation trials confirmed 70 of the primary antiviral hits across both cell systems. Among these validated antivirals, 34 compounds showed activity in both cell types, 25 were specifically active in A549 lung cells, and 11 demonstrated a preference for HUVEC vascular cells.

The study also identified 23 proviral candidates that increased the number of infected cells by up to 400%. The validated antiviral hits were categorized into mechanisms including nucleotide biosynthesis inhibitors, Rapamycin (mTOR) pathway and heat shock protein (HSP90) inhibitors, and Beta-lactam antibiotics. Mycophenolic acid was identified as a nucleotide biosynthesis inhibitor, and Cefodizime was noted as a Beta-lactam antibiotic among the successful candidates.

Orthohantaviruses are rodent-borne viruses that cause zoonotic infections in humans, primarily through the inhalation of aerosols contaminated with rodent excretions. The Puumala virus, discovered in 1980, is the main pathogen responsible for hemorrhagic fever with renal syndrome (HFRS) in Europe. Globally, HFRS is prevalent across Europe and Asia and has an approximate mortality rate of 1%. This distinguishes it from Hantavirus pulmonary syndrome (HPS) in the Americas, which has a documented mortality rate between 30% and 40%.

There are currently no European Medicines Agency (EMA) or U.S. Food and Drug Administration (FDA) approved vaccines or specific treatments available for PUUV infection.