Herbal Medicines as Potential Inhibitors of SARS-CoV-2 Infection.

Coronavirus disease 2019 (COVID-19) is the result of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Understanding molecular pathogenesis is an essential factor for the allocation of effective preventive measures and the development of targeted therapeutics against COVID-19. The genome of SARS-CoV-2 encodes structural and nonstructural proteins, which can be targets for compounds with potential therapeutic ability. On the other hand, the virus life cycle has stages susceptible to targeting by drug compounds. Many natural antiviral compounds have been studied and evaluated at the cellular and molecular levels with antiviral potential. Meanwhile, many studies over the past few months have shown that plant polysaccharides have a good ability to target proteins and stages of the virus life cycle. In this regard, in this review study, the virus specifications and infectious process and structural and functional components of SARSCoV- 2 will be reviewed, and then the latest studies on the effect of plant compounds with more focus on polysaccharides on viral targets and their inhibitory potential on the infectious process of COVID-19 will be discussed.

Assessment of a poly-epitope candidate vaccine against Hepatitis B, C, and poliovirus in interaction with monocyte-derived dendritic cells: An ex-vivo study.

Design and application of epitope-based polyvalent vaccines have recently garnered attention as an efficient alternative for conventional vaccines. We previously have reported the in silico design of HHP antigen which encompasses the immune-dominant epitopes of Hepatitis B surface antigen (HBsAg), Hepatitis C core protein (HCVcp) and Poliovirus viral proteins (VPs). It has been shown that the HHP has desirable conformation to expose the epitopes, high antigenicity and other desired physicochemical and immunological properties. To confirm the accuracy of these predictions, the ex-vivo immunogenicity of the HHP was assessed. The HHP gene was chemically synthesized in pET28a and expressed in E. coli (BL21). The expressed protein was purified and its immunological potency was evaluated on dendritic cells (DCs) as antigen presenting cells (APCs). Functional analysis was assessed in co-cultivation of autologous T-cells with matured DCs (mDCs). T-cell activation, proliferation and cytokines secretion were evaluated using flowcytometry and ELISA methods. Our results indicated that the HHP could induce the DC maturation. The mDCs were able to trigger T-cell activation and proliferation. In silico design and ex-vivo confirmation of immunological potential could pave the way to introduce efficient immunogens for further analysis. The ability of HHP in DC maturation and T-cell activation makes it an amenable vaccine candidate for further in-vivo studies.

Immunoinformatics: In Silico Approaches and Computational Design of a Multi-epitope, Immunogenic Protein.

Immunoinformatics is a new critical field with several tools and databases that conduct the eyesight of experimental selection and facilitate analysis of the great amount of immunologic data obtained from experimental researches and helps to design and introducing new hypothesis. Given these visages, immunoinformatics seems to be the way that develop and progress the immunological research. Bioinformatics methods and applications are successfully employed in vaccine informatics to assist different sites of the preclinical, clinical, and post-licensure vaccine enterprises. On the other hand, the progression of molecular biology and immunology caused epitope vaccines have become the focus of research on molecular vaccines. Moreover, reverse vaccinology could improve vaccine production and vaccination protocols by in silico prediction of protein-vaccine candidates from genome sequences. B- and T-cell immune epitopes could be predicted by immunoinformatics algorithms and computational methods to improve the vaccine design, protective immunity analysis, assessment of vaccine safety and efficacy, and immunization modeling. This review aims to discuss the power of computational approaches in vaccine design and their relevance to the development of effective vaccines. Furthermore, the various divisions of this field and available tools in each item are introduced and reviewed.

The applications of anti-CD20 antibodies to treat various B cells disorders.

B-lymphocyte antigen CD20 (called CD20) is known as an activated-glycosylated phosphoprotein which is expressed on the surface of all B-cells. CD20 is involved in the regulation of trans-membrane Ca2+ conductance and also play critical roles in cell-cycle progression during human B cell proliferation and activation. The appearance of monoclonal antibody (mAb) technology provided an effective field for targeted therapy in treatment of a variety of diseases such as cancer, and autoimmune diseases. Anti-CD20 is one of important antibodies which could be employed in treatment of several diseases. Increasing evidences revealed that efficacy of different anti-CD20 antibodies is implicated by their function. Hence, evaluation of anti-CD20 antibodies function could provide and introduce new anti-CD20 based therapies. In the present study, we summarized several applications of anti-CD20 antibodies in various immune related disorders including B-CLL (B-cell chronic lymphocytic leukemia), rheumatoid arthritis (RA), multiple sclerosis (MS) and melanoma.

DNA vaccine encoding HPV-16 E7 with mutation in L-Y-C-Y-E pRb-binding motif induces potent anti-tumor responses in mice.

Cervical cancer is the second most common cancer among women worldwide and remains a clinical problem despite improvements in early detection and therapy. The human papillomavirus (HPV) type 16 (HPV16) E7 oncoprotein expressed in cervical carcinoma cells are considered as attractive tumor-specific antigen targets for immunotherapy. Since the transformation potential of the oncogenes, vaccination based of these oncogenes is not safe. In present study, DNA vaccine expressing the modified variant with mutation in pRb-binding motif of the HPV-16 E7 oncoprotein was generated. A novel modified E7 gene with mutation in LYCYE motif was designed and constructed and the immunogenicity and antitumor effect of therapeutic DNA vaccines encoding the mutant and wild type of E7 gene were investigated. The L-Y-C-Y-E pRb-binding motif of E7 proteins has been involved in the immortalization and transformation of the host cell. The results showed that the mutant and wild type HPV-16 E7 vectors expressed the desired protein. Furthermore, the immunological mechanism behind mutant E7 DNA vaccine can be attributed at least partially to increased cytotoxic T lymphocyte, accompanied by the up-regulation of Th1-cytokine IFN-γ and TNF-ß and down-regulation of Th3-cytokine TGF-ß. Immunized mice with mutant plasmid demonstrated significantly stronger cell immune responses and higher levels of tumor protection than wild-type E7 DNA vaccine. The results exhibit that modified E7 DNA vaccine may be a promising candidate for development of therapeutic vaccine against HPV-16 cancers.