Prospects for SARS-CoV-2 diagnostics, therapeutics and vaccines in Africa
NATURE REVIEWS MICROBIOLOGY
Authors: Margolin, Emmanuel; Burgers, Wendy A.; Sturrock, Edward D.; Mendelson, Marc; Chapman, Rosamund; Douglass, Nicola; Williamson, Anna-Lise; Rybicki, Edward P.
Abstract
The COVID-19 pandemic has prompted unparalleled progress in the development of vaccines and therapeutics in many countries, but it has also highlighted the vulnerability of resource-limited countries in Africa. Margolin and colleagues review global efforts to develop SARS-CoV-2 diagnostics, therapeutics and vaccines, with a focus on the opportunities and challenges in Africa. The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in a global pandemic, prompting unprecedented efforts to contain the virus. Many developed countries have implemented widespread testing and have rapidly mobilized research programmes to develop vaccines and therapeutics. However, these approaches may be impractical in Africa, where the infrastructure for testing is poorly developed and owing to the limited manufacturing capacity to produce pharmaceuticals. Furthermore, a large burden of HIV-1 and tuberculosis in Africa could exacerbate the severity of infection and may affect vaccine immunogenicity. This Review discusses global efforts to develop diagnostics, therapeutics and vaccines, with these considerations in mind. We also highlight vaccine and diagnostic production platforms that are being developed in Africa and that could be translated into clinical development through appropriate partnerships for manufacture.
Identification of a novel cell-penetrating peptide derived from the capsid protein of chicken anemia virus and its application in gene delivery
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
Authors: Hu, Gaowei; Miao, Yingjie; Luo, Xi; Chu, Wenhui; Fu, Yongqian
Abstract
Cell membranes are a great obstacle for entrance of gene therapeutic agents. Cell-penetrating peptides (CPPs) have been proven as a promising gene delivery tool. However, the early TAT peptide derived from the HIV transcription activator protein has been proven that the sequence contains Furin protease cleaved motifs which limited the TAT application in delivery of exogenous active molecules. In the present study, through the bioinformatics and experimental approach, we have identified a novel CPP derived from the N terminus of VP1 protein of chicken anemia virus (CAV), designated as CVP1-N2, which is rich in arginine residues and contains alpha-helical structure. Then, the ability of CVP1-N2 cell penetrating was detected using confocal imaging and flow cytometry. FITC-labeled CVP1-N2 peptide could rapidly internalize into different types of live cells with dose dependence and without cytotoxic effects by MTT assay. Surprisingly, CVP1-N2 with a pattern of nuclear sub-location has shown the higher uptake efficiency than TAT. At 10, 1, and 0.1 mu M, the mean relative internalization of CVP1-N2 was respectively 1.08-, 12-, and 75-fold higher than that of CVP1, as well as 1.6-, 56-, and 75-fold higher than that of TAT. Moreover, using endocytic inhibitors along with low-temperature stress validated that the CVP1-N2 internalization route is direct translocation pathway. Finally, the capacity of CVP1-N2 for delivery of gene into cells was determined, where it was able to carry red fluorescent protein (RFP) and apoptin genes into cells respectively and induce the apoptosis. All these data indicate that CVP1-N2 could be used as a novel gene delivery vehicle for gene therapy in the future.