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Aim: COVID-19 is currently the biggest threat to mankind. Recently, ivermectin (a US FDA-approved antiparasitic drug) has been explored as an anti-SARS-CoV-2 agent. Herein, we have studied the possible mechanism of action of ivermectin using in silico approaches. Materials & methods: Interaction of ivermectin against the key proteins involved in SARS-CoV-2 pathogenesis were investigated through molecular docking and molecular dynamic simulation. Results: Ivermectin was found as a blocker of viral replicase, protease and human TMPRSS2, which could be the biophysical basis behind its antiviral efficiency. The antiviral action and ADMET profile of ivermectin was on par with the currently used anticorona drugs such as hydroxychloroquine and remdesivir. Conclusion: Our study enlightens the candidature of ivermectin as an effective drug for treating COVID-19.

Helicobacter pylori is a highly potential pathogen to colonize in the human stomach. This bacterial strain is now alarming serious health concern all over the world. Combating through available drugs is a difficult task due to lack of appropriate common targets against genetically diverse strains. Therefore, the developments of effective targets vaccines require alternative strategies to eliminate the H. pylori infection. In this study, we developed a novel vaccine construct using B-cell derived T-cell epitopes from four target antigenic proteins (HpaA, FlaA, FlaB and Omp18), and found the induction of possible immune response using advanced immunoinformatics approaches. In order to boost immune system, we tagged adjuvant (50S ribosomal protein L7/L12) with a suitable linker at the N-terminus side of vaccine sequence. Protein–protein docking between human Toll like receptor 5 (TLR5) and vaccine construct help to predict the way of inductive signaling that leads to immune-response. The calculated negative score (− 151.4, + / − 8.7) of molecular docking complex signify the best binding interface. Molecular dynamics simulation studies confirmed the proper docking between TLR5 and vaccine candidate. Moreover, Normal mode analysis (NMA) calculates the molecular motion of the docking complex. The low eigenvalue (2.935e−05) indicates the stable and flexible molecular motion in the binding interaction side. Finally, in-silico cloning of vaccine candidate was performed using expression vector pET28b (+) with the optimized restriction sites. Supplementary Information The online version of this article (10.1007/s10989-020-10157-w) contains supplementary material, which is available to authorized users.

Recently, a novel coronavirus (SARS‐COV‐2) emerged which is responsible for the recent outbreak in Wuhan, China. Genetically, it is closely related to SARS‐CoV and MERS‐CoV. The situation is getting worse and worse, therefore, there is an urgent need for designing a suitable peptide vaccine component against the SARS‐COV‐2. Here, we characterized spike glycoprotein to obtain immunogenic epitopes. Next, we chose 13 Major Histocompatibility Complex‐(MHC) I and 3 MHC‐II epitopes, having antigenic properties. These epitopes are usually linked to specific linkers to build vaccine components and molecularly dock on toll‐like receptor‐5 to get binding affinity. Therefore, to provide a fast immunogenic profile of these epitopes, we performed immunoinformatics analysis so that the rapid development of the vaccine might bring this disastrous situation to the end earlier., Highlights The potential epitopes of coronavirus (SARS‐CoV‐2) are identified.The docking complex of the construct vaccine and TLR5 is described.Peptide‐based vaccine developed and in silico validation is provided.Common epitopes of coronavirus (SARS‐CoV‐2) against B‐cells and T‐cells are listed.

In spite of the tremendous efforts of the World Health Organization, scientific and medical community to eradicate lymphatic filariasis (LF) within 2020, the disease is still taking a huge toll on mankind throughout the globe. The current therapeutic strategies and solution measures against this alarming condition are suffering from a number of limitations such as inadequate effectiveness of the drugs against the adult-stage parasites, low bioavailability, and emergence of resistance. Considering this situation, development of the new therapeutics are urgently needed to combat human LF, especially targeting the adult filarial nematodes. Brugia malayi, the causative parasite for the human brugian filariasis majorly found in the countries of the South-Asia. In this study, we have designed a vaccine candidate using B-cell and T-cell epitopes derived from the aspartic protease of B. malayi (BmASP-1) and found to display significant humoral and cell mediated immune responses using in-silico approaches. Protein-protein docking between the human Toll-like receptor 4 (TLR4) and the vaccine candidate helped us to predict the way of inductive signaling that leads to immune-response. Molecular dynamics (MD) simulation studies further confirmed the proper docking between the TLR4 and vaccine candidate. Moreover, in-silico cloning of the vaccine element within the expression vector was found useful to optimize the restriction sites as well as to determine the primer location. Taken together, the in-silico vaccine candidate depicted in this study promises could be a useful therapeutic option for treating LF and experimental validation of this study is expected to strengthen the candidature of the said vaccine in the future.

Prostate cancer (PCa) is the second most diagnosed cancer in men and ranked fifth in overall cancer diagnosis. During the past decades, it has arisen as a significant life-threatening disease in men at an older age. At the early onset of illness when it is in localized form, radiation and surgical treatments are applied against this disease. In case of adverse situations androgen deprivation therapy, chemotherapy, hormonal therapy, etc. are widely used as a therapeutic element. However, studies found the occurrences of several side effects after applying these therapies. In current work, several immunoinformatic techniques were applied to formulate a multi-epitopic vaccine from the overexpressed antigenic proteins of PCa. A total of 13 epitopes were identified from the five prostatic antigenic proteins (PSA, PSMA, PSCA, STEAP, and PAP), after validation with several in silico tools. These epitopes were fused to form a vaccine element by (GGGGS)3 peptide linker. Afterward, 5, 6-dimethylxanthenone-4-acetic acid (DMXAA) was used as an adjuvant to initiate and induce STING-mediated cytotoxic cascade. In addition, molecular docking was performed between the vaccine element and HLA class I antigen with the low ACE value of −251 kcal/mol which showed a significant binding. Molecular simulation using normal mode analysis (NMA) illustrated the docking complex as a stable one. Therefore, this observation strongly indicated that our multi epitopes bases peptide vaccine molecule will be an effective candidate for the treatment of the PCa.

Single nucleotide polymorphisms (SNPs) are the most regular type of genetic variation among human genome. The low-density lipoprotein receptors (LDLR) gene encoded receptor protein that specifically binds to low density lipoprotein (LDL), to act as prime cholesterol carriers in the blood. Unregulated removal of LDL from the circulation results from inherited mutations in the LDLR gene or, more rarely, in the apo B gene, the ligand for the LDLR causes familial hypercholesterolemia (FH). Several studies have shown that non-synonymous single nucleotide polymorphisms (nsSNPs) induce more than 50% genetic diseases. However, the growing number of SNPs in databases makes it difficult to evaluate the SNPs that come up with disease development. Therefore, we tried to identify the nsSNP within LDLR gene used mainly computational tools like: PROVEAN, Predict-SNP, SIFT, MAAP, SNAP, PhD-SNP, Polyphen v1, Polyphen v2, PANTHER and nsSNPAnalyzer. After analysing a total of 1114 missense SNPs, we found only 39 nsSNPs are most deleterious, whose conservation score ranges from grade ranges 7 to 9 that is assessed through ConSurf web server. Among 39 most significant nsSNPs, 11were predicted for involving in post translational modifications. Additionally, I-Mutant 2.0 and MUpro tool showed a decreased instability for these nsSNPs upon mutation. Protein structural analysis of these amino acid variants was performed by using I-Mutant 2.0. Stability analysis predicted 11 nsSNPs (C313W, F408K, A431P, A431S, A431T, D433H, D433Y, G546D, G546V, G546E and C697W), these are decreased protein stability. The in-silico analysis in current study may be a significant model for future research design studies.

In 2007, the Michigan Institute for Clinical and Health Research (MICHR) at the University of Michigan received a Clinical and Translational Science Award (CTSA). Within MICHR, the Community Engagement (CE) program supports partnership efforts between researchers, practitioners, and community‐based organizations in specific focal communities throughout Michigan. A key component of the CE program is the Community Engagement Coordinating Council, a group that provides input and guidance on program priorities, strategic planning, and reviews pilot funding proposals for community–academic partnerships. This paper will describe a unique MICHR pilot funding mechanism for Community–University Research Partnerships (CURES) with an emphasis on the ways that community partners are involved in the review process, as well as the benefits, challenges, and insights gained over 5 years of pilot review. There is a growing need for community involvement and expertise in review of funding proposals for community‐engaged research at both institutional and federal levels. The CURES pilot review process is one example of an institutional effort to engage community partners in university funding decisions and has demonstrated clear benefit toward accomplishing the aims of the CTSA.

We present a three-dimensional (3D) digital atlas of a mouse lemur head at 60-micron cubic voxel isotropic resolution. It was constructed from a 3D proton magnetic resonance image (MRI) acquired at 500 MHz. It shows views of 3D volume-rendering and movies of contiguous 2D plane cuts in three orthogonal directions. This MR data set was acquired using a spin-echo pulse sequence under conditions of strong T2 and significant diffusion weighting. Experimental parameters were optimized to provide strong intrinsic contrast between gray and white matter. Familiar anatomical structures are clearly identifiable. Fine fiber tracts, laminations of cortices, details of the inner ears, and layering in the lateral geniculate nuclei are all visible. Anatomical identifications of structures in representative slices selected from the atlas are presented. We also describe some difficulties and trade-offs encountered in microscopic resolution MRI. We note that this type of atlas does not suffer from the spatial distortions and slice registration problems introduced by standard histological techniques. Future in vivo longitudinal studies will provide atlases describing in detail the development of the primate brain.