Marburg virus disease (MVD) caused by the Marburg virus (MARV) generally appears with flu-like symptoms and leads to severe hemorrhagic fever. It spreads via direct contact with infected individuals or animals. Despite being considered to be less threatening in terms of appearances and the number of infected patients, the high fatality rate of this pathogenic virus is a major concern. Until now, no vaccine has been developed to combat this deadly virus. Therefore, vaccination for this virus is necessary to reduce its mortality. Our current investigation focuses on the design and formulation of a multi-epitope vaccine based on the structural proteins of MARV employing immunoinformatics approaches. The screening of potential T-cell and B-cell epitopes from the seven structural proteins of MARV was carried out through specific selection parameters. Afterward, we compiled the shortlisted epitopes by attaching them to an appropriate adjuvant and linkers. Population coverage analysis, conservancy analysis, and MHC cluster analysis of the shortlisted epitopes were satisfactory. Importantly, physicochemical characteristics, human homology assessment, and structure validation of the vaccine construct delineated convenient outcomes. We implemented disulfide bond engineering to stabilize the tertiary or quaternary interactions. Furthermore, stability and physical movements of the vaccine protein were explored using normal-mode analysis. The immune simulation study of the vaccine complexes also exhibited significant results. Additionally, the protein–protein docking and molecular dynamics simulation of the final construct exhibited a higher affinity toward toll-like receptor-4 (TLR4). From simulation trajectories, multiple descriptors, namely, root mean square deviations (rmsd), radius of gyration (Rg), root mean square fluctuations (RMSF), solvent-accessible surface area (SASA), and hydrogen bonds, have been taken into account to demonstrate the inflexible and rigid nature of receptor molecules and the constructed vaccine. Inclusively, our findings suggested the vaccine constructs’ ability to regulate promising immune responses against MARV pathogenesis.

Terminalia chebula Retz, commonly known as ‘Haritaki/Myrobalan,’ has been utilised as a traditional medicine for a long time. It has been extensively exercised in various indigenous medicine practices like Unani, Tibb, Ayurveda, and Siddha to remedy human ailments such as bleeding, carminative, dysentery, liver tonic, digestive, antidiarrheal, analgesic, anthelmintic, antibacterial and helpful in skin disorders. Studies on the pharmacological effects of T. chebula and its phytoconstituents documented between January, 1996 and December, 2021 were explored using various electronic databases. During the time mentioned above, several laboratory approaches revealed the biological properties of T. chebula, including antioxidative, antiproliferative, anti-microbial, proapoptotic, anti-diabetic, anti-ageing, hepatoprotective, anti-inflammatory, and antiepileptic. It is also beneficial in glucose and lipid metabolism and prevents atherogenesis and endothelial dysfunction. Different parts of T. chebula such as fruits, seeds, galls, barks extracted with various solvent systems (aqueous, ethanol, methanol, chloroform, ethyl-acetate) revealed major bioactive compounds like chebulic acid, chebulinic acid, and chebulaginic acid, which in turn proved to have valuable pharmacological properties through broad scientific investigations. There is a common link between chebulagic acid and chebulanin with its antioxidant property, antiaging activity, antiinflammatory, antidiabetic activity, and cardioprotective activity. The actions may be through neutralizing the free radicals responsible for producing tissue damage alongside interconnecting many other diseases. The current review summarises the scientifically documented literature on pharmacological potentials and chemical compositions of T. chebula, which is expected to investigate further studies on this subject.

A pandemic caused by the novel coronavirus (SARS-CoV-2 or COVID-19) began in December 2019 in Wuhan, China, and the number of newly reported cases continues to increase. More than 19.7 million cases have been reported globally and about 728,000 have died as of this writing (10 August 2020). Recently, it has been confirmed that the SARS-CoV-2 main protease (M^pro) enzyme is responsible not only for viral reproduction but also impedes host immune responses. The M^pro provides a highly favorable pharmacological target for the discovery and design of inhibitors. Currently, no specific therapies are available, and investigations into the treatment of COVID-19 are lacking. Therefore, herein, we analyzed the bioactive phytocompounds isolated by gas chromatography–mass spectroscopy (GC-MS) from Tinospora crispa as potential COVID-19 M^pro inhibitors, using molecular docking study. Our analyses unveiled that the top nine hits might serve as potential anti-SARS-CoV-2 lead molecules, with three of them exerting biological activity and warranting further optimization and drug development to combat COVID-19.

Coronavirus disease 2019 (COVID-19), an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been declared a global pandemic by the World Health Organization, and the situation worsens daily, associated with acute increases in case fatality rates. The main protease (M^pro) enzyme produced by SARS-CoV-2 was recently demonstrated to be responsible for not only viral reproduction but also impeding host immune responses. The element selenium (Se) plays a vital role in immune functions, both directly and indirectly. Thus, we hypothesised that Se-containing heterocyclic compounds might curb the activity of SARS-CoV-2 M^pro. We performed a molecular docking analysis and found that several of the selected selenocompounds showed potential binding affinities for SARS-CoV-2 M^pro, especially ethaselen (49), which exhibited a docking score of −6.7 kcal/mol compared with the −6.5 kcal/mol score for GC376 (positive control). Drug-likeness calculations suggested that these compounds are biologically active and possess the characteristics of ideal drug candidates. Based on the binding affinity and drug-likeness results, we selected the 16 most effective selenocompounds as potential anti-COVID-19 drug candidates. We also validated the structural integrity and stability of the drug candidate through molecular dynamics simulation. Using further in vitro and in vivo experiments, we believe that the targeted compound identified in this study (ethaselen) could pave the way for the development of prospective drugs to combat SARS-CoV-2 infections and trigger specific host immune responses.

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), resulting in a contagious respiratory tract infection that has become a global burden since the end of 2019. Notably, fewer patients infected with SARS-CoV-2 progress from acute disease onset to death compared with the progression rate associated with two other coronaviruses, SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV). Several research organizations and pharmaceutical industries have attempted to develop successful vaccine candidates for the prevention of COVID-19. However, increasing evidence indicates that the SARS-CoV-2 genome undergoes frequent mutation; thus, an adequate analysis of the viral strain remains necessary to construct effective vaccines. The current study attempted to design a multi-epitope vaccine by utilizing an approach based on the SARS-CoV-2 structural proteins. We predicted the antigenic T- and B-lymphocyte responses to four structural proteins after screening all structural proteins according to specific characteristics. The predicted epitopes were combined using suitable adjuvants and linkers, and a secondary structure profile indicated that the vaccine shared similar properties with the native protein. Importantly, the molecular docking analysis and molecular dynamics simulations revealed that the constructed vaccine possessed a high affinity for toll-like receptor 4 (TLR4). In addition, multiple descriptors were obtained from the simulation trajectories, including the root-mean-square deviation (RMSD), root-mean-square fluctuation (RMSF), solvent-accessible surface area (SASA), and radius of gyration (R_g), demonstrating the rigid nature and inflexibility of the vaccine and receptor molecules. In addition, codon optimization, based on Escherichia coli K12, was used to determine the GC content and the codon adaptation index (CAI) value, which further followed for the incorporation into the cloning vector pET28+(a). Collectively, these findings suggested that the constructed vaccine could be used to modulate the immune reaction against SARS-CoV-2.