CoVac501, a self-adjuvanting peptide vaccine conjugated with TLR7 agonists, against SARS-CoV-2 induces protective immunity.

Safe, effective, and economical vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are needed to achieve adequate herd immunity and end the pandemic. We constructed a novel SARS-CoV-2 vaccine, CoVac501, which is a self-adjuvanting peptide vaccine conjugated with Toll-like receptor 7 (TLR7) agonists. The vaccine contains immunodominant peptides screened from the receptor-binding domain (RBD) and is fully chemically synthesized. It has been formulated in an optimized nanoemulsion formulation and is stable at 40 °C for 1 month. In non-human primates (NHPs), CoVac501 elicited high and persistent titers of protective neutralizing antibodies against multiple RBD mutations, SARS-CoV-2 original strain, and variants (B.1.1.7 and B.1.617.2). Specific peptides booster immunization against the B.1.351 variant has also been shown to be effective in improving protection against B.1.351. Meanwhile, CoVac501 elicited the increase of memory T cells, antigen-specific CD8+ T-cell responses, and Th1-biased CD4+ T-cell immune responses in NHPs. Notably, at an extremely high SARS-CoV-2 challenge dose of 1 × 107 TCID50, CoVac501 provided near-complete protection for the upper and lower respiratory tracts of cynomolgus macaques.

Sesquiterpenes and polyphenols with glucose-uptake stimulatory and antioxidant activities from the medicinal mushroom Sanghuangporus sanghuang.

A chemical investigation on the fermentation products of Sanghuangporus sanghuang led to the isolation and identification of fourteen secondary metabolites (1-14) including eight sesquiterpenoids (1-8) and six polyphenols (9-14). Compounds 1-3 were sesquiterpenes with new structures which were elucidated based on NMR spectroscopy, high resolution mass spectrometry (HRMS) and electronic circular dichroism (ECD) data. All the isolates were tested for their stimulation effects on glucose uptake in insulin-resistant HepG2 cells, and cellular antioxidant activity. Compounds 9-12 were subjected to molecular docking experiment to primarily evaluate their anti-coronavirus (SARS-CoV-2) activity. As a result, compounds 9-12 were found to increase the glucose uptake of insulin-resistant HepG2 cells by 18.1%, 62.7%, 33.7% and 21.4% at the dose of 50 µmol·L-1, respectively. Compounds 9-12 also showed good cellular antioxidant activities with CAA50 values of 12.23, 23.11, 5.31 and 16.04 µmol·L-1, respectively. Molecular docking between COVID-19 Mpro and compounds 9-12 indicated potential SARS-CoV-2 inhibitory activity of these four compounds. This work provides new insights for the potential role of the medicinal mushroom S. sanghuang as drugs and functional foods.

Self-assembled polymeric micelle as a novel mRNA delivery carrier.

mRNA-based therapy has been evaluated in preclinical and clinical studies for the treatment of a wide variety of disease such as cancer immunotherapies and infectious disease vaccines. However, it remains challenging to development safe and efficient delivery system. Here, we have designed a novel self-assembled polymeric micelle based on vitamin E succinate modified polyethyleneimine copolymer (PVES) to delivery mRNA. In vitro, PVES could transfect mRNA into multiple cell lines such as HEK-293T, HeLa and Vero and the transfection efficiencies were much higher than PEI 25 k. In addition, the cytotoxicity of PVES was much lower than PEI 25 k. Furthermore, mice administered intramuscularly with PVES/SARS-CoV-2 mRNA vaccine induced potent antibody response and show no obvious toxicity. These results demonstrated the potential of PVES as a safe and effective delivery carrier for mRNA.

Effectiveness of corticosteroids to treat severe COVID-19: A systematic review and meta-analysis of prospective studies.

OBJECTIVES: To assess the effects of corticosteroid therapy for patients with severe coronavirus disease 2019 (COVID-19). METHODS: We comprehensively searched articles published in the Cochrane Library, PubMed, Embase, China Biology Medicine (CBM), China National Knowledge Infrastructure (CNKI), Wanfang, and VIP databases from January 1, 2019, to March 20, 2021. RESULTS: A total of 6771 patients from eight prospective studies were included in our meta-analysis. The results showed that corticosteroid therapy was associated with lower mortality in severe COVID-19 (OR = 0.70, 95% CI = 0.54-0.92, P = 0.009; I2 = 54.5%). Since the proportion of the RECOVERY (Randomized Evaluation of COVID-19 Therapy) trial included in the meta-analysis was as high as 71.88%, we removed it and recalculated the pooled OR. The results of the remaining seven studies still suggested such a survival benefit (OR = 0.65, 95% CI = 0.44-0.96, P = 0.030; I2 = 59.8%). Furthermore, subgroup analysis suggested that the pooled OR of three studies using corticosteroids in the early stages of treatment was much lower (OR = 0.37, 95% CI = 0.25-0.57, P < 0.001; I2 = 47.8%). However, after excluding the RECOVERY trial, the pooled OR of the remaining four studies with unspecific administration timing of corticosteroid therapy no longer supported this result (OR = 0.90, 95% CI = 0.69-1.17, P = 0.415; I2 = 0.0%). CONCLUSIONS: In this meta-analysis, evidence based on seven randomized controlled trials and one prospective cohort study indicates that corticosteroid therapy was associated with a reduction in the mortality of severe COVID-19, especially when administered at an earlier time.