EpiCurator: an immunoinformatic workflow to predict and prioritize SARS-CoV-2 epitopes

The ongoing coronavirus 2019 (COVID-19) pandemic, triggered by the emerging SARS-CoV-2 virus, represents a global public health challenge. Therefore, the development of effective vaccines is an urgent need to prevent and control virus spread. One of the vaccine production strategies uses the in silico epitope prediction from the virus genome by immunoinformatic approaches, which assist in selecting candidate epitopes for in vitro and clinical trials research. This study introduces the EpiCurator workflow to predict and prioritize epitopes from SARS-CoV-2 genomes by combining a series of computational filtering tools. To validate the workflow effectiveness, SARS-CoV-2 genomes retrieved from the GISAID database were analyzed. We identified 11 epitopes in the receptor-binding domain (RBD) of Spike glycoprotein, an important antigenic determinant, not previously described in the literature or published on the Immune Epitope Database (IEDB). Interestingly, these epitopes have a combination of important properties: recognized in sequences of the current variants of concern, present high antigenicity, conservancy, and broad population coverage. The RBD epitopes were the source for a multi-epitope design to in silico validation of their immunogenic potential. The multi-epitope overall quality was computationally validated, endorsing its efficiency to trigger an effective immune response since it has stability, high antigenicity and strong interactions with Toll-Like Receptors (TLR). Taken together, the findings in the current study demonstrated the efficacy of the workflow for epitopes discovery, providing target candidates for immunogen development.

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Synthesis and characterization of Chitosan-Catechol conjugates: Development and in vitro, in silico and in vivo evaluation of mucoadhesive pellets of lafutidine

Journal of Bioactive and Compatible Polymers ◽

10.1177/0883911521997849 ◽

2021 ◽

pp. 088391152199784

Author(s):

Loveleen Kaur ◽

Ajay Kumar Thakur ◽

Pradeep Kumar ◽

Inderbir Singh

Keyword(s):

Drug Release ◽

In Silico ◽

Ex Vivo ◽

Strong Interactions ◽

Dissolution Time ◽

Sem Images ◽

In Vivo Evaluation ◽

Release Studies

Present study was aimed to synthesize and characterize Chitosan-Catechol conjugates and to design and develop mucoadhesive pellets loaded with lafutidine. SEM images indicated the presence of fibrous structures responsible for enhanced mucoadhesive potential of Chitosan-Catechol conjugates. Thermodynamic stability and amorphous nature of conjugates was confirmed by DSC and XRD studies respectively. Rheological studies were used to evaluate polymer mucin interactions wherein strong interactions between Chitosan-Catechol conjugate and mucin was observed in comparison to pristine chitosan and mucin. The mucoadhesion potential of Chitosan-Catechol (Cht-C) versus Chitosan (Cht) was assessed in silico using molecular mechanics simulations and the results obtained were compared with the in vitro and ex vivo results. Cht-C/mucin demonstrated much higher energy stabilization (∆E ≈ −65 kcal/mol) as compared to Cht/mucin molecular complex. Lafutidine-loaded pellets were prepared from Chitosan (LPC) and Chitosan-Catechol conjugates (LPCC) and were evaluated for various physical properties viz. flow, circularity, roundness, friability, drug content, particle size and percent mucoadhesion. In vitro drug release studies on LPC and LPCC pellets were performed for computing t50%, t90% and mean dissolution time. The values of release exponent from Korsmeyer-Peppas model was reported to be 0.443 and 0.759 for LPC and LPCC pellets suggesting Fickian and non-Fickian mechanism representing drug release, respectively. In vivo results depicted significant controlled release and enhanced residence of the drug after being released from the chitosan-catechol coated pellets. Chitosan-Catechol conjugates were found to be a promising biooadhesive polymer for the development of various mucoadhesive formulations.

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In vitro antiviral activity of propolis and Baccharis sp. extracts on animal herpesviruses

Arquivos do Instituto Biológico ◽

10.1590/1808-1657000972016 ◽

2018 ◽

Vol 85 (0) ◽

Cited By ~ 1

Author(s):

Isabela Cristina Simoni ◽

Bruna Aguiar ◽

Aline Martineli de Araujo Navarro ◽

Rafael Martins Parreira ◽

Maria Judite Bittencourt Fernandes ◽

...

Keyword(s):

Antiviral Activity ◽

Morphological Changes ◽

Virus Titer ◽

Toxic Concentration ◽

Control Virus ◽

Tetragonisca Angustula ◽

The Difference ◽

Toxic Concentrations ◽

And Control

ABSTRACT: This study evaluated the in vitro antiviral activity of propolis and Baccharis sp. extracts on three animal herpesviruses (bovine, equine and swine). The propolis samples were produced by two species of bees. There was red and green propolis, which came from africanized Apis melifera, and a third type obtained from a native bee species, Tetragonisca angustula (jatai). The Baccharis extracts were obtained from four different species: B. oblongifolia, B. burchellii, B. dracunculifolia and B. uncinella. The maximum non-toxic concentration of the extracts was determined when no visible morphological changes were observed on the cells. These non-toxic concentrations were used in the antiviral tests. Antiviral activity was evaluated using a reduction assay of the cytopathic effect, which calculated the difference between treated and control virus titer by statistical analysis. Red propolis was active against the three herpesviruses and green propolis showed inhibition against the equine and swine herpesviruses. Conversely, jataí propolis showed no antiviral activity. Most extracts coming from male and female individuals of all of the Baccharis species showed antiviral activity against bovine and swine herpesviruses. Only the extract of the female specimen of B. oblongifolia was an inhibitor against equine herpesvirus.

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Synthesis, Characterization, Antibacterial Activity, and Computer-Aided Design of Novel Quinazolin-2,4-dione Derivatives as Potential Inhibitors Against Vibrio cholerae

Evolutionary Bioinformatics ◽

10.1177/1176934319897596 ◽

2020 ◽

Vol 16 ◽

pp. 117693431989759 ◽

Cited By ~ 5

Author(s):

Mohamed El-Naggar ◽

Mahmoud Eldeeb Mohamed ◽

Ahmed Mohamed Mosallam ◽

Wesam Salem ◽

Huda RM Rashdan ◽

...

Keyword(s):

Antibacterial Activity ◽

Vibrio Cholerae ◽

In Silico ◽

Computer Aided Design ◽

Pharmaceutical Chemistry ◽

Strong Interactions ◽

Bacterial Disease ◽

In Silico Docking ◽

Pharmacokinetic Properties

Cholera is a bacterial disease featured by dehydration and severe diarrhea. It is mainly caused by alimentary infection with Vibrio cholerae. Due to the wide applicability of quinazolin-2,4-dione compounds in medicinal and pharmaceutical chemistry, a new series of N-containing heterocyclic compounds was synthesized. We used the in silico docking method to test the efficacy of quinazolin-2,4-dione compounds in the prevention of cholera in humans. The newly synthesized compounds showed strong interactions and good binding affinity to outer membrane protein OmpU. Moreover, the pharmacokinetic properties of the newly synthesized compounds, such as absorption, distribution, metabolic, excretion, and toxicity (ADMET), were predicted through in silico methods. Compounds with acceptable pharmacokinetic properties were tested as novel ligand molecules. The synthesized compounds were evaluated in vitro for their antibacterial activity properties against Gram-negative Escherichia coli O78 strain using the minimum inhibition concentration (MIC) method. Compounds 2 and 6 showed reproducible, effective antibacterial activity. Hence, our study concludes that the quinazolin-2,4-dione derivatives 1 to 8 may be used as promising drug candidates with potential value for the treatment of cholera disease.

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Leishmania spp Epitopes in Humans Naturally Resistant to the Disease: Working Toward a Synthetic Vaccine

Frontiers in Cellular and Infection Microbiology ◽

10.3389/fcimb.2021.631019 ◽

2021 ◽

Vol 11 ◽

Author(s):

Magda Melissa Flórez ◽

Rocío Rodríguez ◽

José Antonio Cabrera ◽

Sara M. Robledo ◽

Gabriela Delgado

Keyword(s):

Immune Response ◽

In Silico ◽

Large Scale ◽

Mononuclear Cells ◽

Clinical Symptoms ◽

Epitope Prediction ◽

Effective Vaccine ◽

Peripheral Blood Mononuclear

Vaccines are one of the most effective strategies to fight infectious diseases. Reverse vaccinology strategies provide tools to perform in silico screening and a rational selection of potential candidates on a large scale before reaching in vitro and in vivo evaluations. Leishmania infection in humans produces clinical symptoms in some individuals, while another part of the population is naturally resistant (asymptomatic course) to the disease, and therefore their immune response controls parasite replication. By the identification of epitopes directly in humans, especially in those resistant to the disease, the probabilities of designing an effective vaccine are higher. The aim of this work was the identification of Leishmania epitopes in resistant humans. To achieve that, 11 peptide sequences (from Leishmania antigenic proteins) were selected using epitope prediction tools, and then, peripheral blood mononuclear cells (PBMCs) were isolated from human volunteers who were previously divided into four clinical groups: susceptible, resistant, exposed and not exposed to the parasite. The induction of inflammatory cytokines and lymphoproliferation was assessed using monocyte-derived dendritic cells (moDCs) as antigen-presenting cells (APCs). The response was evaluated after exposing volunteers’ cells to each peptide. As a result, we learned that STI41 and STI46 peptides induced IL-8 and IL-12 in moDCs and lymphoproliferation and low levels of IL-10 in lymphocytes differentially in resistant volunteers, similar behavior to that observed in those individuals to L. panamensis lysate antigens. We conclude that, in silico analysis allowed for the identification of natural Leishmania epitopes in humans, and also STI41 and STI46 peptides could be epitopes that lead to a cellular immune response directed at parasite control.

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Bio-Mechanism of Catechin as Pheromone Signal Inhibitor: Prediction of Antibacterial Agent Action Mode by In Vitro and In Silico Study

Molecules ◽

10.3390/molecules26216381 ◽

2021 ◽

Vol 26 (21) ◽

pp. 6381

Author(s):

Dikdik Kurnia ◽

Zenika Febian Ramadhanty ◽

Aprilina Mora Ardani ◽

Achmad Zainuddin ◽

Hendra Dian Adhita Dharsono ◽

...

Keyword(s):

Antibiotic Resistance ◽

Binding Energy ◽

Serine Protease ◽

In Silico ◽

Antibacterial Agent ◽

Antibacterial Agents ◽

Chemical Structures ◽

In Silico Study ◽

And Control

The utilization of medicinal plants has long been explored for the discovery of antibacterial agents and the most effective mechanisms or new targets that can prevent and control the spread of antibiotic resistance. One kind of bacterial cell wall inhibition is the inactivation of the MurA enzyme that contributes to the formation of peptidoglycan. Another approach is to interfere with the cell–cell communication of bacteria called the Quorum sensing (QS) system. The blocking of auto-inducer such as gelatinase biosynthesis-activating pheromone (GBAP) can also suppress the virulence factors of gelatinase and serine protease. This research, in particular, aims to analyze lead compounds as antibacterial and anti-QS agents from Gambir (Uncaria gambir Roxburgh) through protein inhibition by in silico study. Antibacterial agents were isolated by bioactivity-guided isolation using a combination of chromatographic methods, and their chemical structures were determined by spectroscopic analysis methods. The in vitro antibacterial activity was evaluated by disc diffusion methods to determine inhibitory values. Meanwhile, in the in silico analysis, the compound of Uncaria gambir was used as ligand and compared with fosfomycin, ambuic acid, quercetin, and taxifolin as the standard ligand. These ligands were attached to MurA, GBAP, gelatinase, and serine proteases using Autodock Vina in PyRx 0.8 followed by PYMOL for combining the ligand conformation and proteins. plus programs to explore the complex, and visualized by Discovery Studio 2020 Client program. The antibacterial agent was identified as catechin that showed inhibitory activity against Enterococcus faecalis ATCC 29212 with inhibition zones of 11.70 mm at 10%, together with MIC and MBC values of 0.63 and 1.25 μg/mL, respectively. In the in silico study, the molecular interaction of catechin with MurA, GBAP, and gelatinase proteins showed good binding energy compared with two positive controls, namely fosfomycin and ambuic acid. It is better to use catechin–MurA (−8.5 Kcal/mol) and catechin–gelatinase (−7.8 Kcal/mol), as they have binding energies which are not marginally different from quercetin and taxifolin. On the other hand, the binding energy of serine protease is lower than quercetin, taxifolin, and ambuic acid. Based on the data, catechin has potency as an antibacterial through the inhibition of GBAP proteins, gelatinase, and serine protease that play a role in the QS system. This is the first discovery of the potential of catechin as an alternative antibacterial agent with an effective mechanism to prevent and control oral disease affected by antibiotic resistance.

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Review on current concepts of myopia and its control strategies

International Journal of Ophthalmology ◽

10.18240/ijo.2021.04.19 ◽

2021 ◽

Vol 14 (4) ◽

pp. 606-615

Author(s):

Raju Kaiti ◽

◽

Indra Prasad Sharma ◽

Manish Dahal ◽

◽

...

Keyword(s):

Control Strategies ◽

Global Public Health ◽

Management Options ◽

Pharmaceutical Management ◽

Significant Burden ◽

Public Health Challenge ◽

Changing Times ◽

Near Work ◽

And Control

Myopia poses a significant burden on the healthcare system, economy and quality of life. It is an emerging global public health challenge and requires interventions to delay or stop onset and progression. With changing times and evidence, the concepts of myopia are changing along with the treatment and control strategies. Behavioural modifications including increased outdoors time and reduced near work, optical and pharmaceutical management options are reviewed. This paper presents a current overview on the concepts of myopia, and is expected to summarize updates on myopia control methods.

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Generation and Evaluation of an African Swine Fever Virus Mutant with Deletion of the CD2v and UK Genes

Vaccines ◽

10.3390/vaccines8040763 ◽

2020 ◽

Vol 8 (4) ◽

pp. 763

Author(s):

Teshale Teklue ◽

Tao Wang ◽

Yuzi Luo ◽

Rongliang Hu ◽

Yuan Sun ◽

...

Keyword(s):

African Swine Fever Virus ◽

Clinical Signs ◽

African Swine Fever ◽

Virus Genome ◽

Fever Virus ◽

Effective Vaccine ◽

Post Inoculation ◽

Virus Mutant ◽

And Control

African swine fever (ASF) is a highly contagious and often lethal disease caused by African swine fever virus (ASFV). ASF emerged in China in August 2018 and has since rapidly spread into many areas of the country. The disease has caused a significant impact on China’s pig and related industries. A safe and effective vaccine is needed to prevent and control the disease. Several gene-deleted ASFVs have been reported; however, none of them is safe enough and commercially available. In this study, we report the generation of a double gene-deleted ASFV mutant, ASFV-SY18-∆CD2v/UK, from a highly virulent field strain ASFV-SY18 isolated in China. The results showed that ASFV-SY18-∆CD2v/UK lost hemadsorption properties, and the simultaneous deletion of the two genes did not significantly affect the in vitro replication of the virus in primary porcine alveolar macrophages. Furthermore, ASFV-SY18-∆CD2v/UK was attenuated in pigs. All the ASFV-SY18-∆CD2v/UK-inoculated pigs remained healthy, and none of them developed ASF-associated clinical signs. Additionally, the ASFV-SY18-∆CD2v/UK-infected pigs developed ASFV-specific antibodies, and no virus genome was detected in blood and nasal discharges at 21 and 28 days post-inoculation. More importantly, we found that all the pigs inoculated with 104 TCID50 of ASFV-SY18-∆CD2v/UK were protected against the challenge with the parental ASFV-SY18. However, low-level ASFV DNA was detected in blood, nasal swabs, and lymphoid tissue after the challenge. The results demonstrate that ASFV-SY18-∆CD2v/UK is safe and able to elicit protective immune response in pigs and can be a potential vaccine candidate to control ASF.

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Identifying SARS-CoV-2 Antiviral Compounds by Screening for Small Molecule Inhibitors of Nsp13 Helicase

10.1101/2021.04.07.438808 ◽

2021 ◽

Author(s):

Rupert Beale ◽

Agustina P Bertolin ◽

Annabel Borg ◽

Berta Canal ◽

John FX Diffley ◽

...

Keyword(s):

High Throughput Screening ◽

Drug Targets ◽

Global Public Health ◽

Chemical Library ◽

Enzymatic Assays ◽

Antiviral Compounds ◽

Public Health Challenge ◽

Related Compounds ◽

Potential Drug Targets

The coronavirus disease 2019 (COVID-19) pandemic, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a global public health challenge. While the efficacy of vaccines against emerging and future virus variants remains unclear, there is a need for therapeutics. Repurposing existing drugs represents a promising and potentially rapid opportunity to find novel antivirals against SARS-CoV-2. The virus encodes at least nine enzymatic activities that are potential drug targets. Here we have expressed, purified and developed enzymatic assays for SARS-CoV-2 nsp13 helicase, a viral replication protein that is essential for the coronavirus life cycle. We screened a custom chemical library of over 5000 previously characterised pharmaceuticals for nsp13 inhibitors using a FRET-based high-throughput screening (HTS) approach. From this, we have identified FPA-124 and several suramin-related compounds as novel inhibitors of nsp13 helicase activity in vitro. We describe the efficacy of these drugs using assays we developed to monitor SARS-CoV-2 growth in Vero E6 cells.

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Computational screening of phytocompounds from Moringa oleifera leaf as potential inhibitors of SARS-CoV-2 Mpro

10.21203/rs.3.rs-71018/v1 ◽

2020 ◽

Author(s):

Athira Nair D ◽

James T J

Keyword(s):

In Silico ◽

Methanolic Extract ◽

Secondary Infection ◽

Virus Multiplication ◽

Global Public Health ◽

Computational Screening ◽

Global Pandemic ◽

Main Protease ◽

Potential Inhibitors

Abstract Background: Coronavirus Disease (COVID-19), caused by novel SARS CoV-2 is rapidly spreading all over the World creating a global public health emergency at unprecedented levels. Till today, no effective treatments or vaccines against this global pandemic is reported and hence to identify lead compounds having potential action in controlling the spread the pandemic is a global concern. This study aimed at in silico screening of phytocompounds from M.oleiera leaf against novel SARS CoV-2 main protease (Mpro) through molecular docking. M.oleiera is an Indian medicinal plant as well as a vegetable, all parts of the plant is medicinally useful and is being used in many of the traditional and Ayurvedic medicinal preparations. Result: When the 19 compounds identified from M.oleifera leaf methanolic extract by Liquid Chromatography Mass Spectrometry (LCMS/MS) analysis and 5 FDA approved anti-viral drugs were screened in silico with SARS CoV-2 main protease (Mpro), the following compounds showed top interaction; apigenin-7-O-rutinoside (-8.8 kcal/mol), Mudanpioside (-8.3 kcal/mol), isoquercetin (-8 kcal/mol), isoquercitrin (-8 kcal/mol), quercetin (-7.8 kcal/mol) and dihydroquercetin (-7.8 kcal/mol). Anti-viral drugs: Raltegravir (-7.2 kcal/mol), Lopinavir-Ritonavir (-7.7 kcal/mol), maraviroc (-8.2 kcal/mol), Nelfinavir (-8.3 kcal/mol) and Tipranavir (-9.2 kcal/mol) also showed active interaction with Mpro. Preliminary phytochemical screening of methanol extract showed the presence of flavonoids, cardiac glycosides, phenols, coumarins, saponins, steroids and phytosteroids. In vitro antioxidant activity of methanolic extract of M.oleifera also showed greater activity, which would ameliorate the post-COVID secondary infection. Conclusion: Hence these compounds from M.oleifera, which are our diet based components, which can interact with the Mpro and curtail COVID-19 virus multiplication in the host cell.

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