The discovery of a new SARS-CoV-2 virus strain in South Africa presents a major public health threat, therefore contributing to increased infections and transmission rates during the second wave of the global pandemic. This study lays the groundwork for the development of a novel subunit vaccine candidate from the circulating strains of South African SARS-CoV-2 and provides an understanding of the molecular epidemiological trend of the circulating strains. A total of 475 whole-genome nucleotide sequences from South Africa submitted between December 1, 2020 and February 15, 2021 available at the GISAID database were retrieved based on its size, coverage level and hosts. To obtain the distribution of the clades and lineages of South African SARS-CoV-2 circulating strains, the metadata of the sequence retrieved were subjected to an epidemiological analysis. There was a prediction of the cytotoxic T lymphocytes (CTL), Helper T cells (HTL) and B-cell epitopes. Furthermore, there was allergenicity, antigenicity and toxicity predictions on the epitopes. The analysis of the physicochemical properties of the vaccine construct was performed; the secondary structure, tertiary structure and B-cell 3D conformational structure of the vaccine construct were predicted. Also, molecular binding simulations and dynamics simulations were adopted in the prediction of the vaccine construct's stability and binding affinity with TLRs. Result obtained from the metadata analysis indicated lineage B.1.351 to be in higher circulation among various circulating strains of SARS-CoV-2 in South Africa and GH has the highest number of circulating clades. The construct of the novel vaccine was antigenic, non-allergenic and non-toxic. The Instability index (II) score and aliphatic index were estimated as 41.74 and 78.72 respectively. The computed half-life in mammalian reticulocytes was 4.4 h in vitro, for yeast and in E. coli was >20 h and >10 h in vivo respectively. The grand average of hydropathicity (GRAVY) score is estimated to be −0.129, signifying the hydrophilic nature of the protein. The molecular docking indicates that the vaccine construct has a high binding affinity towards the TLRs with TLR 3 having the highest binding energy (−1203.2 kcal/mol) and TLR 9 with the lowest (−1559.5 kcal/mol). These results show that the vaccine construct is promising and should be evaluated using animal model.

Fungal infection has become a persistent problem in humans and is sometimes life-threatening in immune-compromised individuals. This work aims to study phytochemicals from Annona muricata (sour sop) as probable antifungal agents against Candida albicans sterol 14α-demethylase target receptor by Computer Aided-Drug Design (CADD) approach using voriconazole and fluconazole as standard drugs. A modern method of drug discovery by molecular docking and chemoinformatics was used to screen 131 isolated phytochemicals with medicinal properties from Annona muricata against Candida albicans ‘sterol 14α-demethylase, a prominent target receptor for most anti-fungal drugs, towards the development of new anti-fungal therapeutic agents and a new approach to treat patients with fungal infections. The compounds were all subjected to analyses like ADMET, drug-likeness, bioactivity, oral-bioavailability and PASS. The results of the docking simulation and chemoinformatics analyses showed that muricin M (-7.9 kcal/mol), chlorogenic acid (-8.2 kcal/mol), roseoside (-8.5 kcal/mol) and caffeoylquinic acid (-8.1 kcal/mol) are potential drug candidates for treating fungal infections due to their excellent properties such as binding affinities, ADMET profile, drug-likeness, bioactivity, binding mode and interactions with the target receptor. Thus, muricin M, chlorogenic acid, roseoside and caffeoylquinic acid are recommended for further analyses towards the development of further antifungal drugs.

No abstract

The bacteria Vibrio cholerae causes cholera, an acute diarrheal infection that can lead to dehydration and even death. Over 100,000 people die each year as a result of epidemic diseases; vaccination has emerged as a successful strategy for combating cholera. This study uses bioinformatics tools to create a multi-epitope vaccine against cholera infection using five structural polyproteins from the V. cholerae (CTB, TCPA, TCPF, OMPU, and OMPW). The antigenic retrieved protein sequence were analyzed using BCPred and IEDB bioinformatics tools to predict B cell and T cell epitopes, respectively, which were then linked with flexible linkers together with an adjuvant to boost it immunogenicity. The construct has a theoretical PI of 6.09, a molecular weight of 53.85 kDa, and an estimated half-life for mammalian reticulocytes in vitro of 4.4 h. These results demonstrate the construct's longevity. The vaccine design was docked against the human toll-like receptor (TLR) to evaluate compatibility and effectiveness; also other additional post-vaccination assessments were carried out on the designed vaccine. Through in silico cloning, its expression was determined. The results show that it has a CAI value of 0.1 and GC contents of 58.97% which established the adequate expression and downstream processing of the vaccine construct, and our research demonstrated that the multi-epitope subunit vaccine exhibits antigenic characteristics. Additionally, we carried out an in silico immunological simulation to examine the immune reaction to an injection. Our results strongly suggest that the vaccine candidate on further validation would induce immune response against the V. cholerae infection.

As the fight against SARS-CoV-2 remains undefeated despite available vaccines, continuous efforts to curtail this deadly and highly spreading virus remain a world priority. In this research, we have investigated the antiviral properties of the phytochemicals from Annona muricata (Sour Sop) as potential inhibitors of SARS-CoV-2 main protease (Mpro) and Spike Receptor Protein. Pharmacokinetic analyses such as in-silicoADME, drug-likeness, PASS prediction, oral-bioavailability and bioactivity were carried out to screen the phytochemicals, 9 out of the 131 ligands satisfied the screening. A molecular docking approach was used to obtain the binding energies of the 9 ligands, and the result showed that Roseoside (−7.50 kcal/mol) and Coreximine (−7.0 kcal/mol) displayed the best docking score and have predicted to have stable interactions with SARS-CoV-2 main protease and Spike Glycoprotein. Data from this study could be further explored in developing multi-target drugs against SARS-CoV-2.