Ongoing COVID-19 outbreak has raised a drastic challenge to global public health security. Most of the patients with COVID-19 suffer from mild flu-like illnesses such as cold and fever; however, few percentages of the patients progress from severe illness to death, mostly in an immunocompromised individual. The causative agent of COVID-19 is an RNA virus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Despite these debilitating conditions, no medication to stop the disease progression or vaccination is available till now. Therefore, we aimed to formulate a multi-epitope vaccine against SARS-CoV-2 by utilizing an immunoinformatics approach. For this purpose, we used the SARS-CoV-2 spike glycoprotein to determine the immunodominant T- and B-cell epitopes. After rigorous assessment, we designed a vaccine construct using four potential epitopes from each of the three epitope classes such as cytotoxic T-lymphocytes, helper T-lymphocyte, and linear B-lymphocyte epitopes. The designed vaccine was antigenic, immunogenic, and non-allergenic with suitable physicochemical properties and has higher solubility. More importantly, the predicted vaccine structure was similar to the native protein. Further investigations indicated a strong and stable binding interaction between the vaccine and the toll-like receptor (TLR4). Strong binding stability and structural compactness were also evident in molecular dynamics simulation. Furthermore, the computer-generated immune simulation showed that the vaccine could trigger real-life-like immune responses upon administration into humans. Finally, codon optimization based on Escherichia coli K12 resulted in optimal GC content and higher CAI value followed by incorporating it into the cloning vector pET28+(a). Overall, these results suggest that the designed peptide vaccine can serve as an excellent prophylactic candidate against SARS-CoV-2. Communicated by Ramaswamy H. Sarma

In recent years, biosynthesized zinc oxide nanoparticles (ZnONPs) have gained tremendous attention because of their safe and non-toxic nature and distinctive biomedical applications. A diverse range of microbes (bacteria, fungi and yeast) and various parts (leaf, root, fruit, flower, peel, stem, etc.) of plants have been exploited for the facile, rapid, cost-effective and non-toxic synthesis of ZnONPs. Plant extracts, microbial biomass or culture supernatant contain various biomolecules including enzymes, amino acids, proteins, vitamins, alkaloids, flavonoids, etc., which serve as reducing, capping and stabilizing agents during the biosynthesis of ZnONPs. The biosynthesized ZnONPs are generally characterized using UV-VIS spectroscopy, TEM, SEM, EDX, XRD, FTIR, etc. Antibiotic resistance is a serious problem for global public health. Due to mutation, shifting environmental circumstances and excessive drug use, the number of multidrug-resistant pathogenic microbes is continuously rising. To solve this issue, novel, safe and effective antimicrobial agents are needed urgently. Biosynthesized ZnONPs could be novel and effective antimicrobial agents because of their safe and non-toxic nature and powerful antimicrobial characteristics. It is proven that biosynthesized ZnONPs have strong antimicrobial activity against various pathogenic microorganisms including multidrug-resistant bacteria. The possible antimicrobial mechanisms of ZnONPs are the generation of reactive oxygen species, physical interactions, disruption of the cell walls and cell membranes, damage to DNA, enzyme inactivation, protein denaturation, ribosomal destabilization and mitochondrial dysfunction. In this review, the biosynthesis of ZnONPs using microbes and plants and their characterization have been reviewed comprehensively. Also, the antimicrobial applications and mechanisms of biosynthesized ZnONPs against various pathogenic microorganisms have been highlighted.

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.

Minichromosome Maintenance Complex Component 7 (MCM7) is a key component of the DNA replication licensing factor and hexamer MCM (MCM2–7) complex that regulates the DNA replication process. The MCM7 protein is associated with tumor cell proliferation that plays an important role in different human cancer progression. As the protein is highly expressed during the cancer development process, therefore, inhibition of the protein can be utilized as a treatment option for different human cancer. However, the study aimed to identify potential small molecular drug candidates against the MCM7 protein that can utilize treatment options for human cancer. Initially, the compounds identified from protein-drugs network analysis have been retrieved from NetworkAnalyst v3.0 server and screened through molecular docking, MM-GBSA, DFT, pharmacokinetics, toxicity, and molecular dynamics (MD) simulation approach. Two compounds namely Dasatinib (CID_3062316) and Bortezomib (CID_387447) have been identified throughout the screening process, which have the highest negative binding affinity (Kcal/mol) and binding free energy (Kcal/mol). The pharmacokinetics and toxicity analysis identified drug-like properties and no toxicity properties of the compounds, where 500 ns MD simulation confirmed structural stability of the two compounds to the targeted proteins. Therefore, we can conclude that the compounds dasatinib and bortezomib can inhibit the activity of the MCM7 and can be developed as a treatment option against human cancer.

Pandemic COVID-19 infections have spread throughout the world. There is no effective treatment against this disease. Viral RNA-dependent RNA polymerase (RdRp) catalyzes the replication of RNA from RNA and the main protease (M^pro) has a role in the processing of polyproteins that are translated from the RNA of SARS-CoV-2, and thus these two enzymes are strong candidates for targeting by anti-viral drugs. Small molecules such as lopinavir and favipiravir significantly inhibit the activity of M^pro and RdRp in vitro. Studies have shown that structurally modified lopinavir, favipiravir, and other similar compounds can inhibit COVID-19 main protease (M^pro) and RNA-dependent RNA polymerase (RdRp). In this study, lopinavir and its structurally similar compounds were chosen to bind the main protease, and favipiravir was chosen to target RNA-dependent RNA polymerase. Molecular docking and the quantitative structure-activity relationships (QSAR) study revealed that the selected candidates have favorable binding affinity but less druggable properties. To improve the druggability, four structural analogues of lopinavir and one structural analogue of favipiravir was designed by structural modification. Molecular interaction analyses have displayed that lopinavir and favipiravir analogues interact with the active site residues of M^pro and RdRp, respectively. Absorption, distribution, metabolism, excretion and toxicity (ADMET) properties, medicinal chemistry profile, and physicochemical features were shown that all structurally modified analogues are less toxic and contain high druggable properties than the selected candidates. Subsequently, 50 ns molecular dynamics simulation of the top four docked complexes demonstrated that CID44271905, a lopinavir analogue, forms the most stable complex with the M^pro. Further MMPBSA analyses using the MD trajectories also confirmed the higher binding affinity of CID44271905 towards M^pro. In summary, this study demonstrates a new way to identify leads for novel anti-viral drugs against COVID-19. Communicated by Ramaswamy H. Sarma