A year of genomic surveillance reveals how the SARS-CoV-2 pandemic unfolded in Africa

The progression of the SARS-CoV-2 pandemic in Africa has so far been heterogeneous and the full impact is not yet well understood. Here, we describe the genomic epidemiology using a dataset of 8746 genomes from 33 African countries and two overseas territories. We show that the epidemics in most countries were initiated by importations, predominantly from Europe, which diminished following the early introduction of international travel restrictions. As the pandemic progressed, ongoing transmission in many countries and increasing mobility led to the emergence and spread within the continent of many variants of concern and interest, such as B.1.351, B.1.525, A.23.1 and C.1.1. Although distorted by low sampling numbers and blind-spots, the findings highlight that Africa must not be left behind in the global pandemic response, otherwise it could become a breeding ground for new variants.

In recent years, molecular modeling has become an important technique for drug discovery and pharmaceutical science. The objective of this study is to determine the molecular modeling of the antibacterial, anti-inflammatory and anti-nociceptive activities of a new series of pyrazoles, oxadiazoles and sugar hydrazines of 5-nitroindolin-2-one derivatives. The molecular modeling protocol was applied using the MOE (Molecular Operating Environment) software. Synthetic compounds 1, 3, 8, 9, 10 and 12 were the most active compounds, as antibacterial, antiinflammatory and anti-nociceptive activities were studied for the binding affinity of the cyclooxygenase1 (COX1), The glucocorticoid receptor (GR), the cytochrome P450 receptor of 14alfa-sterol demethylases (CYP51) and the dihydroprotease synthase receptor. Molecular modeling studies revealed that the [(methylbenzyl)-5-nitro-2-oxoindolin-3-ylideneamino-benzohydrazide derivative (3) gave a score of (-15.8587 kcal/mol), while 1,3,4-oxadiazol-2-yl) phenylimino)-1-(methylbenzyl)-5-nitroindolin-2-one derivative (9) gave a higher score (-16.8038 kcal/mol) than flucanazole Co-crystallized gave a score of (-10.2837 kcal/mol). However, the compound (12), D-Arabinose-(methylbenzyl)-5-nitro-2-oxoindolin-(3-ylideneamino) hydrazone derivative gave a score of (-24.6577 kcal/mol) greater than the co-crystallized ligand which gave a score of (-16.6717 kcal/mol).

Let-7a, miR-34a, and miR-199 a/b have gained a great attention as master regulators for cellular processes. In particular, these three micro-RNAs act as potential onco-suppressors for hepatocellular carcinoma. Bioinformatics can reveal the functionality of these micro-RNAs through target prediction and functional annotation analysis. In the current study, in silico analysis using innovative servers (miRror Suite, DAVID, miRGator V3.0, GeneTrail) has demonstrated the combinatorial and the individual target genes of these micro-RNAs and further explored their roles in hepatocellular carcinoma progression. There were 87 common target messenger RNAs (p ≤ 0.05) that were predicted to be regulated by the three micro-RNAs using miRror 2.0 target prediction tool. In addition, the functional enrichment analysis of these targets that was performed by DAVID functional annotation and REACTOME tools revealed two major immune-related pathways, eight hepatocellular carcinoma hallmarks-linked pathways, and two pathways that mediate interconnected processes between immune system and hepatocellular carcinoma hallmarks. Moreover, protein-protein interaction network for the predicted common targets was obtained by using STRING database. The individual analysis of target genes and pathways for the three micro-RNAs of interest using miRGator V3.0 and GeneTrail servers revealed some novel predicted target oncogenes such as SOX4, which we validated experimentally, in addition to some regulated pathways of immune system and hepatocarcinogenesis such as insulin signaling pathway and adipocytokine signaling pathway. In general, our results demonstrate that let-7a, miR-34a, and miR-199 a/b have novel interactions in different immune system pathways and major hepatocellular carcinoma hallmarks. Thus, our findings shed more light on the roles of these miRNAs as cancer silencers.