To control interspecies transmission of influenza viruses, it is essential to elucidate the molecular mechanisms of the interaction of influenza viruses with sialo-glycoconjugate receptors expressed on different host cells. Competitive inhibitors containing mimetic receptor carbohydrates that prevent virus entry may be useful tools to address such issues. We chemoenzymatically synthesized and characterized the glycopolymers that were carrying terminal 2,6-sialic acid on lactosamine repeats as influenza virus inhibitors. In vitro and in vivo infection experiments using these glycopolymers demonstrated marked differences in inhibitory activity against different species of viruses. Human viruses, including clinically isolated strains, were consistently inhibited by glycopolymers carrying lactosamine repeats with higher activity than those containing a single lactosamine. A swine virus also showed the same recognition properties as those from human hosts. In contrast, avian and equine viruses were not inhibited by any of the glycopolymers examined carrying single, tandem, or triplet lactosamine repeats. Hemagglutination inhibition and solid-phase binding analyses indicated that binding affinity of glycopolymers with influenza viruses contributes dominantly to the inhibitory activity against viral infection. Sequence analysis and molecular modeling of human viruses indicated that specific amino acid substitutions on hemagglutinin may affect binding affinity of glycopolymers carrying lactosamine repeats with viruses. In conclusion, glycopolymers carrying lactosamine repeats of different lengths are useful to define molecular mechanisms of virus recognition. The core carbohydrate portion as well as sialyl linkages on the receptor glycoconjugate may affect host cell recognition of human and swine viruses.

Background: First-generation cephalosporins have good activity against gram-positive bacteria and are extensively used in horses. There are few reports of pharmacokinetics and pharmacodynamics (PK/PD) analysis of cephalosporins in horses.Objective: To optimise the dosages of the two first-generation cephalosporins cephalothin (CET) and cefazolin (CEZ) in horses using PK/PD concepts.Study design: Experimental study with single administration.Methods: Drug plasma concentrations following a single intravenous (i.v.) administration of 22 mg/kg bodyweight (bwt) CET in 12 horses and of 10 mg/kg bwt CEZ in six horses were measured using LC-MS/MS. Data were modelled using a nonlinear mixed effect modelling followed by Monte Carlo simulations. Minimum inhibitory concentrations (MICs) against Streptococcus zooepidemicus and Staphylococcus aureus isolated from horses were determined by the microbroth dilution method. Results:The percentages of CET and CEZ binding to serum proteins were 19.9% ± 8.4% and 15.2% ± 8.5% respectively. For both CET and CEZ, the MIC 90 against S. zooepidemicus was 0.12 mg/L and against S. aureus was 0.5 mg/L. For CET, to achieve a probability of target attainment (PTA) of 90% for a PK/PD target of a free serum plasma concentration exceeding the MIC 90 for 40% of the dosing interval, an empirical CET dosage regimen of 22 mg/kg bwt q8h and 22 mg/kg bwt q4h i.v. administration were required for S. zooepidemicus and S. aureus respectively. For CEZ, the corresponding dosage regimens were 10 mg/kg bwt q12h and 10 mg/kg bwt q8h. Main limitations:Small sample size only in healthy horses. Conclusions:For CET, more frequent administration than that currently recommended (22 mg/kg bwt q6-12h) is required to empirically control S. aureus infection in horses. For CEZ, less frequent administration compared to the dosage regimen

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ObjectiveClinical research on gene therapy has advanced the field of veterinary medicine, and gene doping, which is the illegal use of gene therapy, has become a major concern in horseracing. Since the International Federation of Horseracing Authorities defined the administration of oligonucleotides and its analogues as a genetic therapy in 2017, the development of therapeutic nucleotide-detection techniques has become an urgent need. Most currently marketed and developed oligonucleotide therapeutics for humans consist of modified nucleotides to increase stability, and phosphorothioate (PS) modification is common.ResultsWe demonstrated the specific detection of phosphorothioated oligonucleotides (PSOs) using LC/MS/MS. PSOs produce the specific product ion (m/z 94.9362) derived from PS moiety. PS is not derived from endogenous substances in animal body, and the product ion is a suitable marker for the detection of PSOs. With our strategy, reproducible target analyses were achieved for identifying the specific substances, with a LOD of 0.1 ng/mL and a quantification rage of 0.1–200 ng/mL in deproteinated plasma. Non-target analyses could also detect the presence of PSOs selectively with 100 ng/mL in the same matrix. These results suggested that the detection of PSOs in horse blood is possible by targeting the product ion using LC/MS/MS.Electronic supplementary materialThe online version of this article (10.1186/s13104-018-3885-5) contains supplementary material, which is available to authorized users.

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