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.

Molecular docking and dynamics simulation analysis of nucleoprotein from the Crimea-Congo hemorrhagic fever virus strain Baghdad-12 with FDA approved drugs.

Crimea-Congo hemorrhagic fever virus is considered a potential public health threat due to the high case fatality ratio of the disease hemorrhagic phase and absence of approved vaccines or antiviral agents. Therefore, it is of interest to screen FDA approved drugs against the nucleoprotein crystal of Crimea-Congo hemorrhagic fever virus strain Baghdad-12 by using molecular docking and dynamics simulation. Hence, we report that the beta receptor blocker Nebivolol and the antihistamine Loratadine may bind to RNA binding region on nucleoprotein for further consideration in drug design and development.

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.