Cordycepin Inhibits Enterovirus A71 Replication and Protects Host Cell from Virus-Induced Cytotoxicity through Adenosine Action Pathway.

Enterovirus A71 (EV-A71) infection typically causes mild illnesses, such as hand-foot-and-mouth disease (HFMD), but occasionally leads to severe or fatal neurological complications in infants and young children. Currently, there is no specific antiviral treatment available for EV-A71 infection. Thus, the development of an effective anti-EV-A71 drug is required urgently. Cordycepin, a major bioactive compound found in Cordyceps fungus, has been reported to possess antiviral activity. However, its specific activity against EV-A71 is unknown. In this study, the potency and role of cordycepin treatment on EV-A71 infection were investigated. Results demonstrated that cordycepin treatment significantly reduced the viral load and viral ribonucleic acid (RNA) level in EV-A71-infected Vero cells. In addition, EV-A71-mediated cytotoxicity was significantly inhibited in the presence of cordycepin in a dose-dependent manner. The protective effect can also be extended to Caco-2 intestinal cells, as evidenced by the higher median tissue culture infectious dose (TCID50) values in the cordycepin-treated groups. Furthermore, cordycepin inhibited EV-A71 replication by acting on the adenosine pathway at the post-infection stage. Taken together, our findings reveal that cordycepin could be a potential antiviral candidate for the treatment of EV-A71 infection.

Rapid and highly potent humoral responses to mpox nanovaccine candidates adjuvanted by thermostable scaffolds.

Monkeypox (mpox) is a zoonotic disease caused by monkeypox virus (MPXV) of the orthopoxvirus genus. The emergence and global spread of mpox in 2022 was declared as a public health emergency by World Health Organization. This mpox pandemic alarmed us that mpox still threaten global public health. Live vaccines could be used for immunization for this disease with side effects. New alternative vaccines are urgently needed for this re-emerging disease. Specific antibody responses play key roles for protection against MPXV, therefore, vaccines that induce high humoral immunity will be ideal candidates. In the present study, we developed thermostable nanovaccine candidates for mpox by conjugating MPXV antigens with thermostable nanoscafolds. Three MPXV protective antigens, L1, A29, and A33, and the thermostable Aquafex aeolicus lumazine synthase (AaLS), were expressed in E. coli and purified by Ni-NTA methods. The nanovaccines were generated by conjugation of the antigens with AaLS. Thermal stability test results showed that the nanovaccines remained unchanged after one week storage under 37℃ and only partial degradation under 60℃, indicating high thermostability. Very interesting, one dose immunization with the nanovaccine could induce high potent antibody responses, and two dose induced 2-month high titers of antibodes. In vitro virus neutralization test showed that nanovaccine candidates induced significantly higher levels of neutralization antibodies than monomers. These results indicated that the AaLS conjugation nanovaccines of MPXV antigens are highly thermostable in terms of storage and antigenic, being good alternative vaccine candidates for this re-emerging disease.

Decrease in Dengue virus-2 infection and reduction of cytokine/chemokine production by Uncaria guianensis in human hepatocyte cell line Huh-7

ABSTRACT BACKGROUND Dengue fever may present hemorrhages and cavitary effusions as result of exacerbated immune responses. We investigated hydro-alcoholic extracts from leaves (UGL) and bark (UGB) of the medicinal species Uncaria guinanensis with respect to antiviral effects in Dengue virus (DENV) infection and in immunological parameters associated with in vivo physiopathological features. METHODS Chemical profiles from UGB or UGL were compared in thin layer chromatography and 1H nuclear magnetic resonance using flavonoid compounds and a pentacyclic oxindole alkaloid-enriched fraction as references. DENV-2-infected hepatocytes (Huh-7) were treated with extracts. Cell viability, DENV antigens and immunological factors were detected by enzyme-linked immunosorbent assay (ELISA) or flow cytometry. FINDINGS The UGL mainly differed from UGB by selectively containing the flavonoid kaempferitrin. UGB and UGL improved hepatocyte viability. Both extracts reduced intracellular viral antigen and inhibited the secretion of viral non-structural protein (NS1), which is indicative of viral replication. Reduction in secretion of macrophage migration inhibitory factor was achieved by UGB, of interleukin-6 by UGL, and of interleukin-8 by both UGB and UGL. MAIN CONCLUSIONS The U. guianensis extracts presented, antiviral and immunomodulatory effects for DENV and possibly a hepatocyte-protective activity. Further studies may be performed to consider these products as potential candidates for the development of an herbal product for the future treatment of dengue.

Clinical study of bi yan qing du ke li and nasal care in treatment of patients with nasopharyngeal carcinoma after radiotherapy / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To investigate the effect of bi yan qing du ke li combined with Nasal Care on the titers of EB virus VCA/IgA and nasopharyngeal symptoms in patients with nasopharyngeal carcinoma(NPC) after radiotherapy.@*METHOD@#Sixty NPC patients underwent-radiotherapy were randomly divided into study group (bi yan qing du ke li combined with nasal care, n=30) and control group (bi yan qing du ke li group, n=30).@*RESULT@#After treatment, the geometric mean titer of VCA/IgA was 20.5 in study group and 55.6 in control group, respectively (P < 0.05). Meanwhile, the nasopharyngeal symptoms after treatment in study group was improved significantly better than that of control group (P < 0.05).@*CONCLUSION@#The application of bi yan qing du ke li combined with Nasal Care can significantly decrease the titers of VCA/IgA in NPC patients after-radiotherapy and improve the nasopharyngeal symptoms, which might be helpful to decrease the recurrence rate of NPC.

Immune response induced in mice oral immunization with cowpea severe mosaic virus

There is increasing interest in the immune response induced by plant viruses since these could be used as antigen-expressing systems in vaccination procedures. Cowpea severe mosaic virus (CPSMV), as a purified preparation (300 g of leaves, 2 weeks post-inoculation), or crude extract from cowpea (Vigna unguiculata) leaves infected with CPSMV both administered by gavage to Swiss mice induced a humoral immune response. Groups of 10 Swiss mice (2-month-old females) were immunized orally with 10 daily doses of either 50 æg viral capsid protein (boosters of 50 æg at days 21 and 35 after immunization) or 0.6 mg protein of the crude extract (boosters of 0.6 mg at days 21 and 35 after immunization). Anti-CPSMV antibodies were quantified by ELISA in pooled sera diluted at least 1:400 at days 7, 14, 21, 28, 35 and 42 after the 10th dose. IgG and IgA against CPSMV were produced systemically, but IgE was not detected. No synthesis of specific antibodies against the proteins of leaf extracts from V. unguiculata, infected or not with CPSMV, was detected. The use of CPSMV, a plant-infecting virus that apparently does not induce a pathogenic response in animals, induced a humoral and persistent (at least 6 months) immune response through the administration of low antigen doses by gavage. These results raise the possibility of using CPSMV either as a vector for the production of vaccines against animal pathogens or in quick and easy methods to produce specific antisera for viral diagnosis

Central Neural Pathway for the Rat Tongue / 대한해부학회지

Bartha strain of pseudorabies virus[PRV-Ba] was utilized as a tracer to identify the neuronal axis of rat tongue muscles ; intrinsic muscles and extrinsic muscles, styloglossus, genioglossus, and hyoglossus muscle. After injection of 10 microliter of PRV-Ba into tongue muscles and 48-96 hours survivals, rats were perfused with 4% paraformaldehyde lysine periodate and brains were removed. PRV-Ba were localized in neural circuits by immunohistochemistry employing rabbit anti PRV-Ba as a primary antibody and ABC method. Injection of PRV-Ba into the tongue muscles resulted in uptake and retrograde transport of PRV-Ba in the rat brain. The result showed a circuit specific connection of many nerve cell groups along the time sequence : PRV-Ba immunoreactive cells appeared in hypoglossal nucleus and motor trigeminal nucleus ipsilaterally as seen with conventional tracers. Raphe nucleus, prepositus hypoglossal nucleus, spinal trigeminal nucleus, Al, A5 and facial nucleus of rhombencephalon showed immunoreactivity bilaterally. There were positive neurons in parabrachial nucleus, locus ceruleus, mesencephalic trigeminal nucleus, periaqueductal gray and A7 of mesencephalon and paraventricular nucleus, suprachiasmatic nucleus, organum vasculosum of lamina terminalis of diencephalon. Also positive reactions were showed in amygdala, insular cortex, frontal cortex and subfornical organ in telencephalon. Early immunoreactivity was appeared in hypoglossal nucleus and motor trigeminal nucleus, and there were positive neurons in the nuclei of the medulla oblongate, midbrain, pons, hypothalamus, cerebellum and medial preoptic area at middle stage. Subsequently the viral antigens were found in forebrain cell groups, paraventricular nuclei, suprachiasmatic nucleus, lateral hypothalamic area and primary motor cortex in frontal lobe bilaterally at 80-90hrs postinjection. These data demonstrate that the PRV-Ba can across synapses in the central nervous system with projection specific pattern, and this virus defines many elements of the neural network governing tongue. Therefore PRV-Ba are proved as a excellent neurotracer in the tract-tracing researches.