Background: The development of multi-antibiotic resistant bacteria, especially Gram-negative bacteria which are the major cause of hospital-acquired infections worldwide, had been increasing. Escherichia coli and Klebsiella sp. had become more resistant to different classes of antibiotics, and the treatment of infections caused by these bacteria had developed into a challenge in both developed and developing countries. This study had determined the multi-antibiotic resistance (MAR) patterns of Escherichia coli and Klebsiella sp. isolated from clinical inpatient and outpatient samples. Method: The present study had used 50 E . coli and 48 Klebsiella sp. isolates. Antibiotic susceptibility test had been carried out by using disk diffusion method, and the interpretation of results of the zones of inhibition had accorded with Clinical Laboratory Standards Institute (CLSI). The antibiotics used had included the following: streptomycin, ciprofloxacin, erythromycin, nitrofurantoin, amikacin, gentamicin, ofloxacin, cefepime, oxacillin, colistin sulfate, cefotaxime, ceftazidime, pefloxacine, and cloxacillin. Results: E. coli and K. pneumoniae had shown high-resistance patterns. E. coli had exhibited high resistance against cloxacillin (96%), oxacillin (96%), erythromycin (88%), and most especially streptomycin (98%). Similarly, K. pneumoniae had presented a high resistance to streptomycin (88%), cloxacillin (92%), oxacillin (92%), and colistin (92%). E. coli had presented the highest multidrug resistance with a MAR index of 1.00. A total of 17 E. coli isolates had shown resistance to the 14 antibiotics tested. Conclusion: E. coli and Klebsiella sp. in clinical isolates in outpatients and inpatients in Ibadan, Western Nigeria had demonstrated high antimicrobial resistance. Thus, such condition should be considered a major public health concern, and measures must be taken to establish the sources and drivers of this problem.

Phyloepidemiological approaches have provided specific insight into understanding the emergence and evolution of infection. Knowledge on the outbreak and spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Nigeria would assist in provision of preventive measures to reduce transmission among populations at risk. This study aimed to investigate the evolution of SARS-CoV-2 in Nigeria. A total of 39 complete genomes of SARS-CoV-2 were retrieved from the GISAID EpiFlu™ database on 29 March 2020 to investigate its evolution in Nigeria. Sequences were selected based on the travel history of the individual and the collection date. Other sequences were not selected because they were short, contained artefacts, were not from an original source or had insufficient information. Evolutionary history was inferred using the maximum likelihood method based on the general time reversible model. A phylogenetic tree was constructed to determine the common ancestor of each strain. The phylogenetic analysis showed that the strain in Nigeria clustered in a monophyletic clade with a Wuhan sublineage. Nucleotide alignment also showed a 100% similarity indicating a common origin of evolution. Comparative analysis showed 27 972 (93.6%) identical sites and 97.6% pairwise identity with the consensus. The study evidently showed the entire outbreak of SARS-CoV-2 infection in Nigeria stemmed from a single introduction sharing consensus similarity with the reference SARS-CoV-2 human genome from Wuhan. Preventive measures that can limit the spread of the infection among populations at risk should be implemented.

This article is devoted to applying bioinformatics and immunoinformatics approaches for the development of a multi-epitope mRNA vaccine against the spike glycoproteins of circulating SARS-CoV-2 variants in selected African countries. The study’s relevance is dictated by the fact that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) began its global threat at the end of 2019 and since then has had a devastating impact on the whole world. Measures to reduce threats from the pandemic include social restrictions, restrictions on international travel, and vaccine development. In most cases, vaccine development depends on the spike glycoprotein, which serves as a medium for its entry into host cells. Although several variants of SARS-CoV-2 have emerged from mutations crossing continental boundaries, about 6000 delta variants have been reported along the coast of more than 20 countries in Africa, with South Africa accounting for the highest percentage. This also applies to the omicron variant of the SARS-CoV-2 virus in South Africa. The authors suggest that bioinformatics and immunoinformatics approaches be used to develop a multi-epitope mRNA vaccine against the spike glycoproteins of circulating SARS-CoV-2 variants in selected African countries. Various immunoinformatics tools have been used to predict T- and B-lymphocyte epitopes. The epitopes were further subjected to multiple evaluations to select epitopes that could elicit a sustained immunological response. The candidate vaccine consisted of seven epitopes, a highly immunogenic adjuvant, an MHC I-targeting domain (MITD), a signal peptide, and linkers. The molecular weight (MW) was predicted to be 223.1 kDa, well above the acceptable threshold of 110 kDa on an excellent vaccine candidate. In addition, the results showed that the candidate vaccine was antigenic, non-allergenic, non-toxic, thermostable, and hydrophilic. The vaccine candidate has good population coverage, with the highest range in East Africa (80.44%) followed by South Africa (77.23%). West Africa and North Africa have 76.65% and 76.13%, respectively, while Central Africa (75.64%) has minimal coverage. Among seven epitopes, no mutations were observed in 100 randomly selected SARS-CoV-2 spike glycoproteins in the study area. Evaluation of the secondary structure of the vaccine constructs revealed a stabilized structure showing 36.44% alpha-helices, 20.45% drawn filaments, and 33.38% random helices. Molecular docking of the TLR4 vaccine showed that the simulated vaccine has a high binding affinity for TLR-4, reflecting its ability to stimulate the innate and adaptive immune response.

At this present stage of COVID-19 re-emergence, designing an effective candidate vaccine for different variants of SARS-CoV-2 is a study worthy of consideration. This research used bioinformatics tools to design an mRNA vaccine that captures all the circulating variants and lineages of the virus in its construct. Sequences of these viruses were retrieved across the six continents and analyzed using different tools to screen for the preferable CD8⁺ T lymphocytes (CTL), CD4⁺ T lymphocytes (HTL), and B-cell epitopes. These epitopes were used to design the vaccine. In addition, several other co-translational residues were added to the construct of an mRNA vaccine whose molecular weight is 285.29686 kDa with an estimated pI of 9.2 and has no cross affinity with the human genome with an estimated over 68% to cover the world population. It is relatively stable, with minimal deformability in its interaction with the human innate immune receptor, which includes TLR 3 and TLR 9. The overall result has proven that the designed candidate vaccine is capable of modulating cell-mediated immune responses by activating the actions of CD4⁺ T cells, natural killer cells, and macrophages, and displayed an increased memory T cell and B cell activities, which may further be validated via in vivo and in vitro techniques.

The recent evolution of the SARS-like Coronavirus has ravaged the world. The deadly virus has claimed over millions of lives across the world and hence highlights the need to develop effective therapeutic drugs to contain the disease posed by this parasite. In this study, the inhibitory potential of fifty (50) dietary polyphenols against Coronavirus (SARS-CoV-2) main protease (Mpro) was conducted using the Autodock Vina Molecular docking tool. In the virtual screening process, the binding affinity of Remdesivir (-7.7 kcal/mol) currently used to treat COVID-19 patients was set as the cut-off value to screen out less probable inhibitors. Ellagic acid, Kievitone, and Punicalin were the only promising ligands with binding affinities (-8.9 kcal/mol, -8.0 kcal/mol and -7.9 kcal/mol respectively) lower than the set cut-off value. Furthermore, we validated Ellagic acid and Kievitone efficacy by subjecting them to molecular dynamics simulation and further stability was assessed at the molecular mechanics and quantum levels. The overall analysis indicates both compounds demonstrate higher stability and inhibitory potential to bind to the crucial His41 and Cys145 catalytic dyad of Mpro than the standard drug. However, further analysis of punicalin after evaluating its docking score was not conducted as the ligand pharmacokinetics properties suggests it could pose serious adverse effect to the health of participants in clinical trials. Hence, we employed a more safe approach by filtering out the compound during this study. Conclusively, while Ellagic acid and kievitone polyphenolic compounds have been demonstrated to be promising under this in silico research, further studies are needed to substantiate their clinical relevance.