Molecular docking and dynamics simulation analysis of the human FXIIa with compounds from the Mcule database.

The human factor XIIa is a serine protease enzyme that is implicated in the pathological thrombosis. This coagulation factor represents an interesting molecular target to design safer antithrombotic agents without adversely influencing physiological hemostasis. Therefore, it is of interest to virtually screen the human factor XIIa crystal with millions of compounds in Mcule database in order to identify potential inhibitors. For this purpose, both molecular docking and dynamics simulation were employed to identify potential hits. Also, various predictive approaches were utilized to estimate chemical, pharmacokinetics and toxicological features for the top hits. As such, we report here that compound 4 (1-(4-benzylpiperazin-1-yl)-2-[5-(3,5-dimethylpyrazol-1-yl)-1,2,3, 4-tetrazol-2-yl]ethanone) may be a potential ligand against the human factor XIIa for further consideration in the design and development of novel antithrombotic agents.

Design and construction of multi epitope- peptide vaccine candidate for rabies virus.

Rabies virus is a zoonotic pathogen that causes lethal encephalitis with a case fatality rate of almost 100% in unvaccinated individuals. The currently available vaccines against rabies are composed of inactivated viral particles that only confer a short-term immune response. It is well-known that the entry of rabies virus into host cells is mediated by a trimeric glycoprotein presents on the surface of viral envelope. As the sole viral surface protein, this trimeric glycoprotein represents a promising molecular target to design new vaccines and neutralizing antibodies against rabies virus. Epitope mapping studies had identified several antigenic sites on the surface of trimeric pre-fusion glycoprotein of rabies virus. Therefore, it is of interest to screen the rabies virus glycoprotein by different web-based immuno-informatics tools to identify potential B-cells and T-cells linear epitopes. Here, we present a construct of peptide vaccine that consists of these predicted linear epitopes of rabies virus glycoprotein together with appropriate linkers and adjuvant. Various online prediction tools, molecular docking and dynamics simulation assume that the vaccine construct may be stable, safe and effective. However, validation of these in-silico results is necessary both in vitro and in vivo setting.

Design, synthesis, ADME, biological evaluation and molecular dynamic studies of natural and synthetic remedy of Herpes simplex virus type-1.

Garlic (known as; Allium sativum) is one of the most widely used medicinal plants in the world. Allicin is the major agent of garlic that gives its known pharmacological activities as anti-inflammatory, antibacterial, antifungal, antiviral and antioxidant agent. It could be extracted from bulbs of Allium sativum by water extraction to give allicin in low yield therefore other better methods were followed for extraction such as ultrasonic-assisted method that gives good yield. Attempts to optimize allicin extraction were found with sliced garlic at 25 °C for 90 minute of extraction for maximum yield (112µg/mL). Allicin was subjected to its evaluation as anti-herpetic against herpes simplex virus 1 (HSV-1) and exhibited a promising activity compared to acyclovir which was used as a reference standard. On the other hand, a novel synthetic amantadine derivative was evaluated as antiherpetic agent and prepared from the reaction of 2-thiouracil-5-sulphonyl chloride with amantadine hydrochloride in pyridine. The synergestic effect of allicin and the amantadine derivative was evaluated against HSV-1, using both in silico molecular docking as for dynamics simulations. Thymidine kinase target enzyme was chosen to analyze any possible interactions, as well as any protein-ligand stability. Furthermore, some of properties of the potential HSV-1 thymidine kinase target inhibitor of the amantadine derivative were analyzed.

Towards the design of epitope candidates for Coronavirus 2.

The severe acute respiratory syndrome coronavirus-2, formerly known as 2019 novel coronavirus, is a pandemic public health threat. This beta coronavirus potentially infects the alveolar cells of the lung leading to pneumonia. The disease may progress into acute respiratory distress syndrome especially in elderly patients with comorbidities. Therefore, it is of interest to design and develop candidates for treatment, therapy and prevention. The spike glycoprotein of the virus known to potentially interact with angiotensin converting enzyme 2 as a cell entry receptor is a suitable candidate for further consideration as vaccine and treatment candidate. Hence, we screened the spike protein of coronavirus-2 for potential B-cell and T-cell epitopes for further deliberation. Thus, we document several peptides on the spike protein with predicted high antigenicity, low allergenicity and good stability against selected proteases. The linear B-cell epitope with sequence 'GFNCYFPLQSYGF' is of particular interest in this context towards the design and development of short peptide vaccine candidates for combat and care against the virus.

Molecular docking and dynamics simulation of FDA approved drugs with the main protease from 2019 novel coronavirus.

Design and development of an effective drug to combat the 2019 novel coronavirus remains a challenge. Therefore, it is of interest to study the binding features of 1615 FDA approved drugs with the recently known 2019-nCoV main protease structure having high sequence homology with that from SARS-CoV. We document the binding features of top 10 drugs with the target protein. We further report that Conivaptan and Azelastine are mainly involved in hydrophobic interactions with active site residues. Both drugs can maintain close proximity to the binding pocket of main protease during simulation. However, these data need further in vitro and in vivo evaluation to repurpose these two drugs against 2019-nCoV.