A therapeutic chimeric IgG/IgA expressed by CHO cells for oral treatment of PED in piglets.

Immunoglobulin A (IgA) of sows is critically important for assessing piglets' protective capacity against porcine epidemic diarrhea virus (PEDV). Here, we report a therapeutic chimeric anti-PEDV IgG/IgA expressed by Chinese hamster ovary (CHO) cells for oral treatment of PED. The chimeric anti-PEDV IgG/IgA was produced by the CHO cell lines, in which the heavy chain was constructed by combining the VH, Cγ1 and hinge regions of PEDV IgG mAb 8A3, and the Cα2 and Cα3 domains of a Mus musculus immunoglobulin alpha chain. The chimeric anti-PEDV IgG/IgA could neutralize the strains of CV777 (G1), P014 (G2) and HN1303 (G2) in vitro effectively, showing broad-spectrum neutralization activity. The in vivo challenge experiments demonstrated that chimeric anti-PEDV IgG/IgA (9C4) produced in the CHO cell supernatant could alleviate clinical diarrhea symptoms of the PEDV infection in piglets. In general, our study showed that chimeric anti-PEDV IgG/IgA produced from CHO cell line supernatants effectively alleviates PEDV infection in piglets, which also gives the foundation for the construction of fully functional secretory IgA by the J chain introduction to maximize the antibody therapeutic effect.

A clinically validated, broadly active, oral viral superinfection therapy could mitigate symptoms in early-stage COVID-19 patients.

More than 200 viruses infect humans but drugs are available for fewer than ten. To narrow the gap between 'bugs and drugs', a paradigm shift is required. The "one drug, one bug" approach should be supplemented by the "one drug, multiple bugs" strategy such that the host is targeted rather than the virus. The revolutionary viral superinfection therapy (SIT) activates the antiviral interferon gene natural defense system of host cells from within by an attenuated infectious bursal disease virus (IBDV) that releases its double-stranded RNA (dsRNA) cargo inside the cells. An attenuated IBDV vaccine strain has resolved hepatitis A virus infection (HAV) in marmoset monkeys and hepatitis B and C virus infections (HBV/HCV) in 42 patients with acute HBV or HCV. SIT was also safe and effective in four hepatically decompensated, chronically infected HBV and HCV patients. The proof-of-principle of SIT was demonstrated first in a 43-year-old male patient with COVID-19. Three doses of IBDV (3x106 IU) alleviated most of his COVID-19 symptoms, even the sense of smell returned within a week. Two additional COVID-19 patients responded similarly to oral treatment with IBDV. Furthermore, a severe herpes zoster ophthalmicus with orbital edema was healed within few days by combination of acyclovir and 7 doses IBDV (7x106 IU). IBDV is simple to manufacture and will be affordable even in resource limited settings. Acid resistant IBDV can be orally administered in an outpatient setting providing the greatest ease of dosing and the highest chance of patient compliance. Under an Emergency Use Authorization, the broad-based IBDV drug candidate could be tested immediately in clinical trials and rapidly distributed to millions of early-stage patients with COVID-19. The German Paul Ehrlich Institute supports such a phase I safety study for persons acutely infected with SARS­CoV-2. An expert team of the US National Institutes of Health-sponsored ACTIV public-private partnership came to the conclusion that the IBDV drug candidate shows merit as a potential treatment for COVID-19 and an FDA approved clinical trial is in the pipelines in Los Angeles.

Nirmatrelvir and Ritonavir Tablets (Paxlovid)

INDICATIONS NIR/RIT can be prescribed to treat mild-to-moderate COVID-19 in patients age 12 years and older weighing at least 40 kg with positive results of direct SARS-CoV-2 testing who are at high risk for progression to severe COVID-19, including hospitalization or death.1 NIR/RIT is not indicated for pre-exposure or post-exposure prevention of COVID-19. < 1%).1 COMMENTS NIR inhibition of the Mpro prevents replication of SARS-CoV-2.1 Data supporting the EUA for NIR/RIT was a Phase II/III randomized, double-blind, placebo-controlled study.1 Subjects were nonhospitalized, symptomatic adults with laboratory-confirmed diagnosis of SARS-CoV-2 infection at risk for progression to severe disease. Risk factors included diabetes, BMI > 25 kg/m2, chronic lung disease, chronic kidney disease, current smoker, immunosuppressive disease/immunosuppressive treatment, cardiovascular disease, hypertension, sickle cell disease, neurodevelopmental disorders, active cancer, or ≥ age 60 years regardless of comorbidities.

COVID-19: a novel coronavirus and a novel challenge for oral healthcare.

OBJECTIVES: Explore how to manage oral healthcare during the COVID-19 outbreak. MATERIALS AND METHODS: In order to solve oral healthcare during the COVID-19 outbreak, our hospital has taken effective measures: build a team of experts, which provide a 24-h hotline, online video consultation, and online training and push popular science articles on WeChat. For the treatment of emergency patients aside from routine epidemic prevention measures, some special measures for oral treatment need to be added. RESULTS: From January 23, 2020, to March 2, 2020, a total of 3035 patients received oral therapy during the COVID-19 epidemic in our hospital. To our knowledge, no oral health worker or patient has been infected with COVID-19 due to oral treatment, and no patients have complained about the suspension of treatment by complaints hotline. CONCLUSION: COVID-19 is a novel challenge for oral healthcare. Attention should be paid to oral healthcare during the outbreak of COVID-19. CLINICAL RELEVANCE: These experiences of oral healthcare can be used as a reference by stomatological hospitals and oral clinics during public health emergencies.