Structure-Based Virtual Screening, Molecular Docking, Molecular Dynamics Simulation of EGFR for the Clinical Treatment of Glioblastoma.

Glioblastoma (GBM) is a WHO Grade IV tumor with poor visibility, a high risk of comorbidity, and exhibit limited treatment options. Resurfacing from second-rate glioma was originally classified as either mandatory or optional. Recent interest in personalized medicine has motivated research toward biomarker stratification-based individualized illness therapy. GBM biomarkers have been investigated for their potential utility in prognostic stratification, driving the development of targeted therapy and customizing therapeutic treatment. Due to the availability of a specific EGFRvIII mutational variation with a clear function in glioma-genesis, recent research suggests that EGFR has the potential to be a prognostic factor in GBM, while others have shown no clinical link between EGFR and survival. The pre-existing pharmaceutical lapatinib (PubChem ID: 208,908) with a higher affinity score is used for virtual screening. As a result, the current study revealed a newly screened chemical (PubChem CID: 59,671,768) with a higher affinity than the previously known molecule. When the two compounds are compared, the former has the lowest re-rank score. The time-resolved features of a virtually screened chemical and an established compound were investigated using molecular dynamics simulation. Both compounds are equivalent, according to the ADMET study. This report implies that the virtual screened chemical could be a promising Glioblastoma therapy.

A Review on Pharmacokinetics Properties of Antiretroviral Drugs to Treat HIV-1 Infections.

BACKGROUND: The HIV-1 pandemic is undoubtedly the major public-health crisis of our time. The extensive research on HIV has deepened our understanding of its pathogenesis and transmission dynamics. Some new entity molecules have been approved by the FDA for HIV treatment, but till now, the protective vaccine remains elusive. Scientists are targeting many important proteins of HIV-1; gp41, gp120, CCR5 coreceptor, integrase, reverse transcriptase and protease. Few compounds are used as nucleotide analogues to stop HIV replication. Altogether, these compounds and their derivatives specifically block HIV entry and DNA replication. Using ADMET studies, people are working on these compounds to reduce toxicity and increase potency. OBJECTIVES: Our main aim is to discuss the Pharmacokinetics properties of 23 important FDA antiretroviral drugs used for the treatment of HIV-1 infections. METHODS: We have searched literature related to pharmacokinetics properties in PubMed, Google Scholar search engine. CONCLUSION: Here, we have reviewed the pharmacokinetic properties such as absorption, bioavailability, distribution, metabolism, and excretion of 23 important FDA-approved drugs. These drugs are Fuzeon, Selzentry, Complera, Epivir, Retrovir, Emtriva, Ziagen, Edurant, Intelence, Pifeltro, Sustiva, Viramune, Isentress, Genvoya, Tivicay, Reyataz, Prezista, Lexiva, Invirase, Aptivus etc. classified into five major classes: fusion inhibitors, Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (NRTIs), Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs), Integrase Strand transfer inhibitors (INSTIs) and Protease inhibitors (PIs). This review may be helpful for the future development of potent antiretroviral drugs with improved pharmacokinetic properties.

Constitutive Inflammatory Cytokine Storm: A Major Threat to Human Health.

Immune cells secrete small protein molecules that aim for cell-cell communications. These small molecules are called cytokines. Targeting cancer cells with administration of bispecific antibodies and natural extracts results in elevated circulating levels of inflammatory cytokines, including interferon-γ and interleukin (IL)-6, which lead to cell toxicity. Sustained release of cytokines due to immunotherapy or hormonal issues causes various diseases. Novel T cell-engaging therapies and monoclonal antibodies cause cytokine release syndrome. Efforts are being carried out to maximize the chance for therapeutic benefit from immunotherapy while minimizing the risk for life-threatening complications of sustained cytokine release. Neurodegeneration and cardiac diseases are the prominent diseases caused by inflammatory cytokines. The phenomenon is called cytokine storm. Cytokines can act antagonistically or synergistically. Constitutive expression of proinflammatory cytokines such as IL-3 and IL-6 causes organ damage and unbearable pain. In this review, we will discuss the regulators of cytokine release, its types, its implications on human health, and treatment.