Résumé
Investment in Africa over the past year with regards to SARS-CoV-2 genotyping has led to a massive increase in the number of sequences, exceeding 100,000 genomes generated to track the pandemic on the continent. Our results show an increase in the number of African countries able to sequence within their own borders, coupled with a decrease in sequencing turnaround time. Findings from this genomic surveillance underscores the heterogeneous nature of the pandemic but we observe repeated dissemination of SARS-CoV-2 variants within the continent. Sustained investment for genomic surveillance in Africa is needed as the virus continues to evolve, particularly in the low vaccination landscape. These investments are very crucial for preparedness and response for future pathogen outbreaks.
Résumé
The molecular mechanisms underlying the pathogenesis of COVID-19 has not been fully discovered. This study aims to decipher potentially hidden parts of the pathogenesis of COVID-19, potential novel drug targets, and to identify potential drug candidates. Two gene expression profiles (GSE147507-GSE153970) were analyzed and overlapping differentially expressed genes (DEGs) were selected for which top enriched transcription factors and kinases were identified and pathway analysis was performed. Protein-protein interaction (PPI) of DEGs was constructed, hub genes were identified and module analysis was also performed. DGIdb database was used to identify drugs for the potential targets (hub genes and the most enriched transcription factors and kinases for DEGs). A drug-potential target network was constructed and drugs are ranked according to the degree. L1000FDW web-based utility was used to identify drugs that can reverse transcriptional profiles of COVID-19. We identified drugs currently in clinical trials and novel potential 8 drugs. Besides the well-known pathogenic pathways, It was found that axon guidance is a potential pathogenic pathway. Sema7A, which may exacerbate hypercytokinemia, is considered a potential novel drug target. Another potential novel pathway is related to TINF2 overexpression which may induce potential telomere dysfunction and hence DNA damage that may exacerbate lung fibrosis.
Sujets)
COVID-19Résumé
Computational prediction of immunogenic epitopes is a promising platform for therapeutic and preventive vaccine design. A potential target for this strategy is human immunodeficiency virus (HIV-1), for which, despite decades of efforts, no vaccine is available. In particular, a therapeutic vaccine devised to eliminate infected cells would represent a key component of cure strategies. HIV peptides designed based on individual viro-immunological data from people living with HIV/AIDS have recently shown able to induce post-therapy viral set point abatement. However, the reproducibility and scalability of this method is curtailed by the errors and arbitrariness associated with manual peptide design as well as by the time-consuming process. We herein introduce Custommune, a user-friendly web tool to design personalized and population-targeted vaccines. When applied to HIV-1, Custommune predicted personalized epitopes using patient specific Human Leukocyte Antigen (HLA) alleles and viral sequences, as well as the expected HLA-peptide binding strength and potential immune escape mutations. Of note, Custommune predictions compared favorably with manually designed peptides administered in a recent phase II clinical trial ( NCT02961829 ). Furthermore, we utilized Custommune to design preventive vaccines targeted for populations highly affected by COVID-19. The results allowed the identification of peptides tailored for each population and predicted to elicit both CD8 + T-cell immunity and neutralizing antibodies against structurally conserved epitopes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Overall, our data describe a new tool for rapid development of personalized or population-based immunotherapy against chronic and acute viral infections.