The epidermal growth factor receptor (EGFR) belongs to the ERBB family of tyrosine kinase receptors. EGFR signaling cascade is a key regulator in cell proliferation, differentiation, division, survival, and cancer development. In this review, the EGFR structure and its mutations, signaling pathway, ligand binding and EGFR dimerization, EGF/EGFR interaction, and the progress in the development of EGFR inhibitors have been explored.

Myocarditis and pericarditis have been linked recently to COVID-19 vaccines without exploring the underlying mechanisms, or compared to cardiac adverse events post-non-COVID-19 vaccines. We introduce an informatics approach to study post-vaccine adverse events on the systems biology level to aid the prioritization of effective preventive measures and mechanism-based pharmacotherapy by integrating the analysis of adverse event reports from the Vaccine Adverse Event Reporting System (VAERS) with systems biology methods. Our results indicated that post-vaccine myocarditis and pericarditis were associated most frequently with mRNA COVID-19 vaccines followed by live or live-attenuated non-COVID-19 vaccines such as smallpox and anthrax vaccines. The frequencies of cardiac adverse events were affected by vaccine, vaccine type, vaccine dose, sex, and age of the vaccinated individuals. Systems biology results suggested a central role of interferon-gamma (INF-gamma) in the biological processes leading to cardiac adverse events, by impacting MAPK and JAK-STAT signaling pathways. We suggest that increasing the time interval between vaccine doses minimizes the risks of developing inflammatory adverse reactions. We also propose glucocorticoids as preferred treatments based on system biology evidence. Our informatics workflow provides an invaluable tool to study post-vaccine adverse events on the systems biology level to suggest effective mechanism-based pharmacotherapy and/or suitable preventive measures.

Coronavirus Disease 2019 (COVID-19) is a contagious disease that affects the respiratory system. In addition to the severe effects of the disease on health, the pandemic caused a negative impact on basic needs and services, employment, education, and economy worldwide. In Jordan, the whole country locked down, and quarantine was enforced by the military forces, which successfully controlled the spread of the disease. This research aims to study the influence of the COVID-19 pandemic and its associated quarantine on university students' beliefs about online learning practice in Jordan. An online descriptive survey involved questions that covered students' demographic information, student's basic and advanced knowledge about COVID-19, students' online learning experience during the quarantine, and finally students' views on the enforced quarantine practice in Jordan. Results showed that students have a good knowledge (>50%) about the COVID-19 basic information and a moderate knowledge (<50%) regarding COVID-19 advanced information. In general, students were pessimistic about the future of COVID-19 both locally and worldwide. Although some students acknowledged that they learned new skills in the fields of electronics, informatics, and computer software during the pandemic, most of them were unsatisfied about the quality and quantity of the given material, online exams, and the evaluation processes. Unfortunately, most of the students faced internet technical problems or challenges to electronic accessibility. The majority of the participants (>90%) supported the military-enforced quarantine implemented in the country despite the hard time the students had during the quarantine. We conclude that university students were able to protect themselves from COVID-19 through their good knowledge about the infectious disease and their commitment to follow the rules imposed by the Government of Jordan. Nevertheless, the challenges caused by the pandemic and its associated quarantine, combined with the sudden unprecedented online experience, negatively impacted students' thoughts and beliefs about the online learning experience during the quarantine. Further studies need to be performed in this context. We hope our results will help decision-makers better understand the students' attitudes and motivation toward online learning and how this will affect their future plans and decisions.

There is accumulating evidence in the biomedical literature suggesting the role of smoking in increasing the risk of oral diseases including some oral cancers. Smoking alters microbial attributes of the oral cavity by decreasing the commensal microbial population and increasing the pathogenic microbes. This study aims to investigate the shift in the salivary microbiota between smokers and non-smokers in Jordan. Our methods relied on high-throughput next-generation sequencing (NGS) experiments for V3-V4 hypervariable regions of the 16S rRNA gene, followed by comprehensive bioinformatics analysis including advanced multidimensional data visualization methods and statistical analysis approaches. Six genera—Streptococcus, Prevotella, Vellionella, Rothia, Neisseria, and Haemophilus—predominated the salivary microbiota of all samples with different percentages suggesting the possibility for the salivary microbiome to restored after quitting smoking. Three genera—Streptococcus, Prevotella, and Veillonella—showed significantly elevated levels among smokers at the expense of Neisseria in non-smokers. In conclusion, smoking has a definite impact on shifting the salivary microbiota in smokers. We can suggest that there is microbial signature at the genera level that can be used to classify smokers and non-smokers by Linear Discriminant Analysis Effect Size (LEfSe) based on the salivary abundance of genera. Proteomics and metabolomics studies are highly recommended to fully understand the effect of bacterial endotoxin release and xenobiotic metabolism on the bacterial interrelationships in the salivary microbiome and how they affect the growth of each other in the saliva of smokers.

Recently, an outbreak of a fatal coronavirus, SARS-CoV-2, has emerged from China and is rapidly spreading worldwide. Possible interaction of SARS-CoV-2 with DPP4 peptidase may partly contribute to the viral pathogenesis. An integrative bioinformatics approach starting with mining the biomedical literature for high confidence DPP4-protein/gene associations followed by functional analysis using network analysis and pathway enrichment was adopted. The results indicate that the identified DPP4 networks are highly enriched in viral processes required for viral entry and infection, and as a result, we propose DPP4 as an important putative target for the treatment of COVID-19. Additionally, our protein-chemical interaction networks identified important interactions between DPP4 and sitagliptin. We conclude that sitagliptin may be beneficial for the treatment of COVID-19 disease, either as monotherapy or in combination with other therapies, especially for diabetic patients and patients with pre-existing cardiovascular conditions who are already at higher risk of COVID-19 mortality.

We have devised a chemocentric informatics methodology for drug discovery integrating independent approaches to mining biomolecular databases. As a proof of concept, we have searched for novel putative cognition enhancers. First, we generated Quantitative Structure- Activity Relationship (QSAR) models of compounds binding to 5-hydroxytryptamine-6 receptor (5HT6R), a known target for cognition enhancers, and employed these models for virtual screening to identify putative 5-HT6R actives. Second, we queried chemogenomics data from the Connectivity Map (http://www.broad.mit.edu/cmap/) with the gene expression profile signatures of Alzheimer’s disease patients to identify compounds putatively linked to the disease. Thirteen common hits were tested in 5-HT6R radioligand binding assays and ten were confirmed as actives. Four of them were known selective estrogen receptor modulators that were never reported as 5-HT6R ligands. Furthermore, nine of the confirmed actives were reported elsewhere to have memory-enhancing effects. The approaches discussed herein can be used broadly to identify novel drug-target-disease associations.

Some antipsychotic drugs are known to cause valvular heart disease by activating serotonin 5-HT2B receptors. We have developed and validated binary classification QSAR models capable of predicting potential 5-HT2B binders. The classification accuracies of the models to discriminate 5-HT2B actives from the inactives were as high as 80% for the external test set. These models were used to screen in silico 59,000 compounds included in the World Drug Index and 122 compounds were predicted as actives with high confidence. Ten of them were tested in radioligand binding assays and nine were found active suggesting a success rate of 90%. All validated binders were then tested in functional assays and one compound was identified as a true 5-HT2B agonist. We suggest that the QSAR models developed in this study could be used as reliable predictors to flag drug candidates that are likely to cause valvulopathy.

: Coronaviruses (CoVs) are enveloped positive-stranded RNA viruses with spike (S) protein projections that allow the virus to enter and infect host cells. The S protein is a key virulence factor determining viral pathogenesis, host tropism, and disease pathogenesis. There are currently diverse corona viruses that are known to cause disease in humans. The occurrence of Middle East respiratory syndrome coronavirus (MERS-CoV) and Severe Acute Respiratory Syndrome coronavirus (SARS-CoV), as fatal human CoV diseases, has induced significant interest in the medical field. The novel coronavirus disease (COVID-19) is an infectious disease caused by a novel strain of coronavirus (SAR-CoV-2). The SARSCoV2 outbreak has been evolved in Wuhan, China, in December 2019, and identified as a pandemic on March 2020 resulting in 53.24 M cases and 1.20M deaths worldwide. SARS-CoV-2 main proteinase (MPro), a key protease of CoV-2, mediates viral replication and transcription. SARS-CoV-2 MPro has been emerged as an attractive target for SARS-CoV-2 drug design and development. Diverse scaffolds have been released targeting SARS-CoV-2 MPro. In this review, we culminate the latest published information about SARS-CoV-2 main proteinase (MPro) and reported inhibitors.