A novel infectious agent, SARS-CoV-2, is responsible for causing the severe respiratory disease COVID-19 and death in humans. Spike glycoprotein plays a key role in viral particles entering host cells, mediating receptor recognition and membrane fusion, and are considered useful targets for antiviral vaccine candidates. Therefore, computational techniques can be used to design a safe, antigenic, immunogenic, and stable vaccine against this pathogen. Drawing upon the structure of the S glycoprotein, we are trying to develop a potent multi-epitope subunit vaccine against SARS-CoV-2. The vaccine was designed based on cytotoxic T-lymphocyte and helper T-lymphocyte epitopes with an N-terminal adjuvant via conducting immune filters and an extensive immunoinformatic investigation. The safety and immunogenicity of the designed vaccine were further evaluated via using various physicochemical, allergenic, and antigenic characteristics. Vaccine-target (toll-like receptors: TLR2 and TLR4) interactions, binding affinities, and dynamical stabilities were inspected through molecular docking and molecular dynamic (MD) simulation methods. Moreover, MD simulations for dimeric TLRs/vaccine in the membrane-aqueous environment were performed to understand the differential domain organization of TLRs/vaccine. Further, dynamical behaviors of vaccine/TLR systems were inspected via identifying the key residues (named HUB nodes) that control interaction stability and provide a clear molecular mechanism. The obtained results from molecular docking and MD simulation revealed a strong and stable interaction between vaccine and TLRs. The vaccine's ability to stimulate the immune response was assessed by using computational immune simulation. This predicted a significant level of cytotoxic T cell and helper T cell activation, as well as IgG, interleukin 2, and interferon-gamma production. This study shows that the designed vaccine is structurally and dynamically stable and can trigger an effective immune response against viral infections.

The ongoing pandemic situation of COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a global threat to both the world economy and public health. Therefore, there is an urgent need to discover effective vaccines or drugs to fight against this virus. The flavonoids and their medicinal plant sources have already exhibited various biological effects, including antiviral, anti-inflammatory, antioxidant, etc. This study was designed to evaluate different flavonoids from medicinal plants as potential inhibitors against the spike protein (Sp) and main protease (M^pro) of SARS-CoV-2 using various computational approaches such as molecular docking, molecular dynamics. The binding affinity and inhibitory effects of all studied flavonoids were discussed and compared with some antiviral drugs that are currently being used in COVID-19 treatment namely favipiravir, lopinavir, and hydroxychloroquine, respectively. Among all studies flavonoids and proposed antiviral drugs, luteolin and mundulinol exhibited the highest binding affinity toward Mpro and Sp. Drug-likeness and ADMET studies revealed that the chosen flavonoids are safe and non-toxic. One hundred ns-MD simulations were implemented for luteolin-Mpro, mundulinol-Mpro, luteolin-Sp, and mundulinol-Sp complexes and the results revealed strong stability of these flavonoid-protein complexes. Furthermore, MM/PBSA confirms the stability of luteolin and mundulinol interactions within the active sites of this protein. In conclusion, our findings reveal that the promising activity of luteolin and mundulinol as inhibitors against COVID-19 via inhibiting the spike protein and major protease of SARS CoV-2, and we urge further research to achieve the clinical significance of our proposed molecular-based efficacy.

As an omnipresent opportunistic bacterium, Pseudomonas aeruginosa PAO1 is responsible for acute and chronic infection in immunocompromised individuals. Currently, this bacterium is on WHO’s red list where new antibiotics are urgently required for the treatment. Finding essential genes and essential hypothetical proteins (EHP) can be crucial in identifying novel druggable targets and therapeutics. This study is aimed at characterizing these EHPs and analyzing subcellular and physiochemical properties, PPI network, nonhomologous analysis against humans, virulence factor and novel drug target prediction, and finally structural analysis of the identified target employing around 42 robust bioinformatics tools/databases, the output of which was evaluated using the ROC analysis. The study discovered 18 EHPs from 336 essential genes, with domain and functional annotation revealing that 50% of these proteins belong to the enzyme category. The majority are cytoplasmic and cytoplasmic membrane proteins, with half being stable proteins subjected to PPIs network analysis. The network contains 261 nodes and 269 edges for 9 proteins of interest, with 11 hubs containing at least three nodes each. Finally, a pipeline builder predicts 7 proteins with novel drug targets, 5 nonhomologous proteins against human proteome, human antitargets, and human gut flora, and 3 virulent proteins. Among these, homology modeling of NP_249450 and NP_251676 was done, and the Ramachandran plot analysis revealed that more than 94% of the residues were in the preferred region. By analyzing functional attributes and virulence characteristics, the findings of this study may facilitate the development of innovative antibacterial drug targets and drugs of Pseudomonas aeruginosa PAO1.

The coronavirus disease 2019 (COVID-19), a life-threatening pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has resulted in massive destruction and is still continuously adding to its death toll. The advent of this global outbreak has not yet been confirmed; however, investigation for suitable prophylaxis against this lethal virus is being carried out by experts all around the globe. The SARS-CoV-2 belongs to the Coronaviridae superfamily, like the other previously occurring human coronavirus variants. To better understand a new virus variant, such as the SARS-CoV-2 delta variant, it is vital to investigate previous virus strains, including their genomic composition and functionality. Our study aimed at addressing the basic overview of the virus’ profile that may provide the scientific community with evidence-based insights into COVID-19. Therefore, this study accomplished a comprehensive literature review that includes the virus’ origin, classification, structure, life cycle, genome, mutation, epidemiology, and subsequent essential factors associated with host–virus interaction. Moreover, we summarized the considerable diagnostic measures, treatment options, including multiple therapeutic approaches, and prevention, as well as future directions that may reduce the impact and misery caused by this devastating pandemic. The observations and data provided here have been screened and accumulated through extensive literature study, hence this study will help the scientific community properly understand this new virus and provide further leads for therapeutic interventions.

Candida auris is an emerging multidrug-resistant fungal pathogen. However, little is known about the role of long noncoding RNAs (lncRNAs) in the human immune response to this fungus. This study aimed to identify and prioritize novel lncRNAs associated with the response of human peripheral blood mononuclear cells (PBMCs) to C. auris and its cell wall components. We reanalyzed RNA-sequencing data from peripheral blood mononuclear cells obtained from three healthy donors. The cells were exposed to live C. auris , purified mannan, purified β-glucan, or RPMI control for 4 h or 24 h. We identified 607 putative novel polyadenylated lncRNA loci that were absent from GENCODE Release 48. Of the 449 novel loci tested for differential expression, 102 responded to at least one stimulus. Novel-lncRNA responses were limited at 4 h but increased markedly at 24 h. At 24 h, 78 novel lncRNAs responded to live C. auris , 34 to mannan, and 11 to β-glucan. Many of these responses are specific to a particular stimulus. Among the 102 responsive lncRNAs, 94 were significantly coexpressed with protein-coding genes. The coding genes of the most highly connected lncRNAs were associated with innate immunity, defense responses, lysosomal functions, and signaling pathways. Temporal analysis revealed 19 novel lncRNAs whose responses changed between 4 and 24 h. Fourteen novel lncRNAs were also differentially expressed and were selected for further analysis. Combining temporal response, coexpression, and genomic proximity identified 4 candidate cis-associated pairs: MSTRG.32011-TLR2, MSTRG.5763-DUSP5, MSTRG.25627-HCK, and MSTRG.18159-ITGB3. These findings reveal a predominantly late and stimulus-specific novel-lncRNA response to C. auris and provide prioritized candidates for experimental validation.