Canine distemper (CD) is an acute infectious disease with high morbidity rates caused by a highly contagious pathogen (Canine Morbillivirus, also known as canine distemper virus, CDV). CDV can infect a broad range of carnivores resulting in complex clinical signs. Currently, there is no effective method to treat for CDV infections. Favipiravir (T-705), a pyrazine derivative, was shown to be an effective antiviral drug against RNA viruses, acting on RNA-dependent RNA polymerase (RdRp). However, whether the T-705 has antiviral effects following CDV infection is unclear. Here, we investigated the antiviral effect of T-705 against CDV-3 and CDV-11 strains in Vero and DH82 cell lines. Our data demonstrated that T-705 significantly inhibited the replication of CDV-3 and CDV-11 in both Vero and DH82 cells at different concentrations, ranging from 2.441 μg/ml to 1250 μg/ml. Additionally, T-705 exhibited efficacious antiviral effects when administered at different time points after virus infection. Cytotoxicity tests showed a slight decline in viability in Vero cells after T-705 treatment, and no apparent cytotoxicity was detected in T-705 treated DH82 cells. Comparison of anti-CDV polyclonal serum only inhibition of CDV in supernatant, T-705 directly inhibited viral replication in cells, and indirectly reduced the amount of virions in supernatant. The combination application of T-705 and anti-CDV polyclonal serum exhibited a rapid and robust inhibition against virions in supernatant and virus replication in cells. Our data strongly indicated that T-705 effectively inhibited viral replication following CDV infection in vitro, and could be a potential candidate for treatment for CD.

Estrogen deficiency in postmenopausal women is accompanied by immune status alterations, leading to a chronic low-grade inflammatory phenotype. Immediate rabies postexposure prophylaxis (PEP) following a transdermal bite or scratch from a rabies-infected animal is urgently needed. However, whether immune alterations in postmenopausal women influence the reaction to rabies vaccination remains unclear. Bilateral ovariectomized (OVX) and Sham mice were immunized with modified live vaccine RABV LBNSE. LBNSE immunization had no obvious pathological effect on the mice in either group and effectively protected all mice from RABV attack. Although 100% protection was found, the reduction rate of viral neutralizing antibody titers in the LBNSE-OVX mice was greater than that in the LBNSE-Sham mice. LBNSE immunization recruited/activated fewer dendritic cells (DCs) and B cells in the lymph nodes, while more B cells were detected in the blood of LBNSE-OVX mice than in that of LBNSE-Sham mice. Th1 and Th2 immune responses are both rapidly induced in LBNSE-OVX-subjected mice and are inclined toward a Th2-biased immune response. LBNSE immunization in OVX mice elicited similar amounts of RABV-specific CD4 ⁺ and CD8 ⁺ T cells as those in Sham mice. Our data revealed that the protective efficacy of rabies vaccination was slightly decreased by estrogen deficiency and that DC and B lymphocyte recruitment/activation and Th-mediated responses in splenocytes were partly altered; however, rabies vaccination offered sufficient protection against RABV within the observation period, helping alleviate anxiety related to rabies virus exposure after menopause. Additional measures might be helpful to improve long-term effective protection in postmenopausal women. IMPORTANCE: Menopause has a distinct effect on the decrease in the female immune system, and whether protection efficacy after rabies vaccination in postmenopausal women is influenced requires evaluation. Our findings demonstrated that although viral neutralizing antibody (VNA) titers in the LBNSE-OVX mice were similar to those in the LBNSE-Sham mice, VNAs declined faster than those in the LBNSE-Sham mice within the observation period. Fewer dendritic cells in the lymph nodes were recruited/activated in LBNSE-OVX mice than in LBNSE-Sham mice, whereas B cells in the lymph nodes and peripheral blood exhibited the opposite tendency. Th2-biased immune responses were induced in LBNSE-OVX mice, and no significant changes were observed in RABV-specific CD4 ⁺ or CD8 ⁺ T cells. These results provide evidence that rabies vaccination could provide effective protection for postmenopausal women within the observation period, but other measures might be needed to improve protection, which is beneficial for alleviating anxiety of menopausal women when facing rabies immunization.

Opaganib is a proprietary, host-directed, potentially broadly potent, first-in-class oral sphingosine kinase 2 (SphK2) selective inhibitor developed by RedHill Biopharma Tel Aviv, Israel. It is currently the most widely used selective SphK2 inhibitor. It simultaneously inhibits three sphingolipid-metabolizing enzymes in human cells—SphK2, dihydroceramide desaturase (DES1), and glucosylceramide synthase (GCS)—leading to depletion of sphingosine 1-phosphate (S1P), accumulation of ceramides and dihydroceramides, and suppression of key pro-survival pathways including pERK, pAKT, and NF-κB. These events promote autophagy, apoptosis, and disruption of viral replication. A large body of evidence indicates that SphK plays an important role in health and disease. This study reviews the role and mechanisms of opaganib effects as anticancer, anti-inflammatory, and antiviral agent. The latest research directions for opaganib are described as gastrointestinal acute radiation syndrome (GI-ARS), chemical exposure indications, and COVID-19, Ebola, and other viruses, providing new therapeutic ideas and considerations for future research and clinical trials.