IL-2 is a powerful immune growth factor and it plays important role in sustaining T cell response. The potential of IL-2 in expanding T cells without loss of functionality has led to its early use in cancer immunotherapy. IL-2 has been reported to induce complete and durable regressions in cancer patients but immune related adverse effects have been reported (irAE). The present review discusses the prospects of IL-2 in immunotherapy for cancer.
In this study, the isolation, the structural characterization, and the elucidation of the biosynthetic origin of heterobactins, catecholate-hydroxamate mixed-type siderophores from Rhodococcus erythropolis PR4, are reported. The structure elucidation of heterobactin A was accomplished via MS(n) analysis and NMR spectroscopy and revealed the noteworthy presence of a peptide bond between the guanidine group of an arginine residue and a 2,3-dihydroxybenzoate moiety. The two heterobactin S1 and S2 variants are derivatives of heterobactin A that have sulfonation modifications on the aromatic rings. The bioinformatic analysis of the R. erythropolis PR4 genome and the subsequent genetic and biochemical characterization of the putative biosynthetic machinery identified the gene cluster responsible for the biosynthesis of the heterobactins. Interestingly, the HtbG NRPS presents an unprecedented C-PCP-A domain organization within the second module of the synthetase that may help the correct elongation of the peptide intermediate. Finally, the present work revises the structure of heterobactin A that was described by Carrano et al. in 2001.
The first case of Middle East respiratory syndrome coronavirus (MERS-CoV) was identified in the year 2012, which spread rapidly and increased to more than 2200 in 2018. This highly pathogenic virus with high mortality rate is among one of the major public health concerns. Saudi Arabia remains to be the most affected region with the majority of MERS-CoV cases, and currently, no effective drugs and vaccines are available for prevention and treatment. A large amount of information is now available regarding the virus, its structure, route of transmission and its pathophysiology. Therefore, this review summarizes the current understanding of MERS-CoV's pathogenesis, treatment options and recent scientific advancements in vaccine and other therapeutic developments, and the major steps taken for MERS prevention control. Coronaviruses are positive stranded RNA viruses, and while most of these infect animals, particularly bats, a minor number can also cause human diseases [16]. Human coronaviruses can be broadly divided into types, α and β coronavirus [17]. MERS-CoV is from the β-coronavirus family [18]. It has four major surface proteins that help the virus to enter the cells viz. envelope protein (E), spike (S) protein, nucleocapsid (N) protein and membrane (M) protein. The spike (S) protein is a transmembrane glycoprotein made up of S1 and S2 subunits. The S protein is crucial for virus entry through binding and fusion to host cells. The S1 subunit has a receptor binding domain (RBD) that binds with the DPP4 receptor of the host [18,19]. The S2 subunit contains heptad repeats H1 and H2 which forms the main membrane fusion unit [20]. The E protein is required for assembly, intracellular transport and budding of virus [21]. The M protein has its role in viral morphogenesis and assembly [22]. N proteins and S, E and M proteins interact to form complete virus particles [23]. In addition to these structural proteins, MERS-CoV has two large polyproteins called pp1a and pp1ab. These proteins are broken down by proteases to form various nonstructural essential proteins, such as enzymes [24,25]. Recent studies have revealed that these viral structural and nonstructural proteins can be exploited as novel targets for therapeutic purposes [26][27][28]. Clinical presentationThe infection caused by MERS-CoV has an average incubation time of 5 days (2-14 days range). The host, in this time period, shows no symptoms of infection. The clinical symptoms of the disease range from mild symptoms of upper respiratory infection like cough, fever and myalgia to severe forms such as pneumonitis, as well as respiratory failure. Patients may also suffer from abdominal pain, appetite loss, nausea, diarrhea, vomiting and other gastrointestinal symptoms. The less commonly occurring symptoms include hemoptysis and diarrhea without any hint of fever [29]. Studies advocate that chronic illnesses, such as chronic heart disease, kidney disease, diabetes and hypertension, increase the risk of MERS-CoV infection and its severity [30], though further proo...
Zika flavivirus is suspected to cause Guillain-Barre syndrome in adults and microcephaly, along with other congenital abnormalities in infants. Presently, no vaccines or therapeutics are available. Here, we report novel compounds identified by high-throughput virtual screening of Maybridge chemical database and molecular docking studies. We selected viral enzyme NS2B/NS3 serine protease as the therapeutic target because of its important role in viral replication. We selected seven potential compounds as antiviral drug candidates because of their high GOLD fitness score, high AutoDock Vina score, or X-Score binding energy and analyzed the strength of molecular interactions between the active site amino acids and selected compounds. Our study also provides a foundation for similar studies for the search of novel therapeutics against Zika virus.
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