Yongtao Li

Coronaviruses (family Coronaviridae) are enveloped, positive-sense, single-stranded RNA viruses with broad host adaptability. They transmit across species among humans, livestock, companion animals, and wildlife, eliciting a disease spectrum ranging from mild respiratory and gastrointestinal symptoms to fatal multi-organ failure, thereby posing significant challenges to global health. In this context, drug repurposing has emerged as a practical strategy for rapidly identifying broad-spectrum antivirals against emerging and re-emerging coronaviruses. Using coronaviruses as a paradigm, this review systematically summarizes research advances and mechanistic insights into the repurposing of existing drugs against coronaviruses. Simultaneously, we dissect core challenges including species-specific pharmacokinetic disparities, insufficient inter-genera conservation of viral targets, and systemic barriers between human and veterinary drug regulatory frameworks and propose innovative solutions encompassing AI-driven cross-species drug prediction, next-generation cross-species infection models, and a “human-veterinary dual-track” collaborative research and development system. Collectively, this review highlights the promise of drug repurposing as a broad-spectrum antiviral strategy and provides a translational perspective for the development of cross-species anti-coronavirus therapeutics.

Feline panleukopenia virus (FPV) is a major feline pathogen, but canine-derived FPV variants have recently been identified. Here, we compared the pathogenicity of a canine-derived FPV strain in cats with that of a lethal feline-derived FPV strain and evaluated the evolutionary significance of its NS1 mutations. Kittens infected with the canine-derived strain developed only mild, self-limiting diarrhea without fever or mortality, whereas those infected with the feline-derived strain developed severe disease and reached humane endpoints by 9 dpi. The canine-derived strain caused prolonged fecal shedding from 6 to 38 dpi but only low tissue viral loads (10¹–10³ copies/g), while the feline-derived strain reached markedly higher loads (10³–10⁶ copies/g), particularly in the ileum, jejunum, and lungs. Viral DNA levels in the lungs, ileum, caecum, and rectum were significantly higher in the feline-derived group. Sequence analysis identified four NS1 mutations, 115I, 132L, 247Q, and 595Q, which showed stepwise evolutionary accumulation and signatures of positive selection. These findings indicate that canine-derived FPV retains infectivity in cats but exhibits attenuated pathogenicity and reduced replication fitness, highlighting NS1 as a potential determinant of host adaptation.

Porcine epidemic diarrhea virus (PEDV) continues to pose a significant threat to the swine industry, leading to high mortality in neonatal piglets and substantial economic losses. The emergence of antigenic variants often compromises vaccine efficacy, highlighting the need for novel antiviral strategies. This study investigates the potential of 4-octyl itaconate (4-OI) as a novel therapeutic agent against PEDV. In vitro studies demonstrated that 4-OI exhibits dose-dependent antiviral activity across multiple cell lines, directly inactivates the virus, and displays broad-spectrum inhibitory effects against enveloped viruses. In a piglet model, 4-OI administration (100 mg/kg) significantly reduced disease severity, as evidenced by decreased intestinal viral load and tissue damage, improved weight gain, reduced diarrhea, and enhanced survival. Mechanistically, 4-OI inhibits PEDV replication by modulating both the NRF2–SLC7A11–ferroptosis axis and the mTOR–ATG5–autophagy pathway, thereby preventing the virus from exploiting the host autophagy–ferroptosis interplay.These findings suggest that 4-OI is a promising therapeutic candidate for PEDV infection, offering a novel host-targeted antiviral approach. Simultaneously targeting SLC7A11 opens up a promising new direction for antiviral therapy.

The spread of Getah virus (GETV) in China has become increasingly severe due to long‐term neglect and the lack of vaccines, posing a threat to animal safety and public health. In this study, we isolated and identified a novel GETV strain, designated GETV‐CX7. Phylogenetic analysis of the E2 gene and the complete genome showed that GETV‐CX7 belongs to Group III. Notably, sequence analysis revealed a novel 14‐nucleotide deletion near the 5 ^’ end of the 3 ^’ untranslated region (UTR) of GETV‐CX7. RNA Secondary Structure Package (RNAfold) predictions further revealed that this deletion changes the RNA secondary structure of the 3 ^’ UTR in GETV‐CX7. Additionally, pathogenicity experiments demonstrated 100% mortality in mice infected with GETV‐CX7 via subcutaneous or intracerebral routes. GETV‐CX7‐infected mice exhibited tissue lesions, including hemorrhaging in the brain, lungs, and kidneys, as well as intestinal wall thinning. GETV‐CX7 exhibits broad tissue tropism, particularly in the brain, with a viral load of up to 6.2 log ₁₀ PFU/g by 3 days postchallenge (dpc). In summary, we isolated a novel GETV Group III strain, GETV‐CX7, characterized by a 14‐nt deletion in the 3 ^’ UTR, which exhibited high pathogenicity in 5‐day‐old mice.

The devastating impact of porcine epidemic diarrhea virus (PEDV) on the global swine industry underscores an urgent need for effective antiviral therapies. Drug repurposing presents a promising strategy to accelerate the development of such treatments. In this study, we screened a custom‐designed library of 117 cholesterol‐lowering compounds for anti‐PEDV activity using a recombinant PEDV expressing enhanced green fluorescent protein (EGFP). Following two rounds of screening, four compounds exhibiting significant antiviral activity were identified. Among these, cetaben and digitonin displayed superior antiviral efficacy and higher selectivity indices. Subsequent dose–response analyses further confirmed that cetaben effectively suppresses viral replication in both classical and variant strains of PEDV. Time‐of‐addition assays revealed that cetaben exerts potent antiviral effects primarily at the preinfection stage by inhibiting viral internalization and syncytium formation. Notably, supplementation with exogenous cholesterol in infected cells completely abolished cetaben’s antiviral activity and restored viral infectivity, demonstrating that its anti‐PEDV mechanism is mediated through disruption of cellular cholesterol metabolism. Collectively, our findings identify cetaben, a cholesterol‐lowering agent, as a novel broad‐acting antiviral against PEDV with a host‐targeted mechanism of action. This study establishes a foundation for developing antiviral strategies that target cholesterol metabolism to combat PEDV and related coronaviruses.

In May 2025, a female giraffe in poor body condition died unexpectedly at a zoo in Henan Province, China. A bacterial strain, designated HN-1, was isolated from the heart, liver, spleen, lungs, and kidneys of the deceased animal. After 24 h of incubation at 37 °C on Luria–Bertani (LB) agar, the colonies appeared round, smooth, pale yellow, translucent, and raised. Gram staining revealed that the isolate was a Gram-positive, rod-shaped, and non-spore-forming bacterium. Based on 16S rRNA gene sequencing, the strain showed more than 99.7% homology with reference sequences of E. mexicanum from various sources in GenBank. The results of the susceptibility test showed that E. mexicanum was susceptible to levofloxacin, clindamycin, chloramphenicol, trimethoprim, rifampicin, tetracycline, minocycline, gentamicin, erythromycin, and doxycycline, but resistant to oxacillin, penicillin, ciprofloxacin, and linezolid. These findings provide valuable insights for the diagnosis and treatment of infections caused by E. mexicanum in giraffes.

In May 2025, a female giraffe in poor body condition died unexpectedly at a zoo in Henan Province, China. A bacterial strain, designated HN-1, was isolated from the heart, liver, spleen, lungs, and kidneys of the deceased animal. After 24 hours of incubation at 37°C on Luria–Bertani (LB) agar, the colonies appeared round, smooth, pale yellow, translucent, and raised. Gram staining revealed that the isolate was a Gram-positive, rod-shaped, and non-spore-forming bacterium. Based on 16S rRNA gene sequencing, the strain showed more than 99.7% homology with reference sequences of E. mexicanum from various sources in GenBank. The results of the susceptibility test showed that E. mexicanum was susceptible to levofloxacin, clindamycin, chloramphenicol, trimethoprim, rifampicin, tetracycline, minocycline, gentamicin, erythromycin, and doxycycline, but resistant to oxacillin, penicillin, ciprofloxacin, and linezolid. These findings provide valuable insights for the diagnosis and treatment of infections caused by E. mexicanum in giraffes.

Sun Y, et al. J Vet Sci. 2025 Mar;26:e26. https://doi.org/10.4142/jvs.24243