Design of small molecules with HIV fusion inhibitory property based on Gp41 interaction assay

Gp41 of HIV [Human Immunodeficiency Virus] is a protein that mediates fusion between viral and cellular membranes. The agent, T-20, which has been approved for HIV inhibition, can restrain Gp41 function in the fusion process; nevertheless, it has disadvantages like instability, high cost of production and injection form to be delivered twice a day. Several molecules like NB-2 and NB-64 have been discovered that can inhibit HIV infection. These molecules were used as template compounds to design and develop more effective small molecules functioning as HIV-1 fusion inhibitors targeting Gp41. The process included in silico docking protocols using HEX and ArgusLab applications. A multisource database was created, after choosing the best molecules; they were tested in vitro for inhibitory activity by HIV-1 single-cycle model, transfected in HEK cells [293T]. Computational analysis and experimental data were combined to explore molecular properties and the most potent ones were found, with the best suitable criteria for interaction with Gp41. Several examples [DAA-6, DAA-9 and DAA-12] could inhibit infection in vitro as effective as NB-2, NB- 64. Since disadvantages of available fusion inhibitor [T-20], it seems necessary to find similar molecules to be approved and have small size providing suitable bioactivity profile. The molecules explored in this study can be good candidates for further investigations to be used as oral HIV fusion inhibitors in the future

Human rotavirus genotypes detection among hospitalized children, a study in Tehran, Iran

Background: human rotavirus genotypes G1-G4, G9, P [4] and P [8] are major worldwide causes of acute gastroenteritis in children. Rotavirus genotype G1P [8] is predominant in many countries. In this study, the genotypic diversity of group A rotaviruses were detected in children <5 years of age who were treated for dehydration and diarrhea in Tehran, Iran from October 2004 to September 2008

Methods: a total of 700 stool specimens were collected from children and assessed for the presence of rotaviruses by the dsRNA-PAGE technique. G and P typing of the positive samples were performed by semi-nested multiplex RT-PCR

Results: rotaviruses were isolated in 19% of samples. A total of 14 rotavirus dsRNA different electrophoretypes were detected. The predominant genotype was G1 [76.3%], followed by G4 [11.5%], G8 [0.8%], P [4] [9.2%] and P [8] [66.4%], respectively. In mixed type samples, the majority were of genotype G1P [8] [53.4%], followed by G1P [4] [9.2%] and G4P [8] [4.6%]. Mixed types consisted of 3.1% of the total sample followed by G1G2/-P [1.5%], G1G4P [4] [0.8%] and G1G4P [8] [0.8%]

Conclusion: in this study, a high prevalence of the G1P [8] genotype was determined to be the cause of childhood gastroenteritis in Tehran, Iran. The sequence of G and P genotypes showed high levels of similarity to strains from other Asian countries. Our data will be useful for future vaccine formulation in Iran

Phylogenetic comparison of influenza virus isolates from three medical centers in Tehran with the vaccine strains during 2008-2009

Influenza virus is a major infectious pathogen of the respiratory system causing a high degree of morbidity and mortality annually. The worldwide vaccines are decided and produced annually by The Worldwide vaccines are decided and produced annually by World Health Organization and licensed companies based on the samples collected from all over the world. The aim of this study was to determine phylogenecity and heterogenecity of the circulating influenza isolates during 2008-2009 outbreaks in Tehran, compare them with the vaccine strains that were recommended by WHO for the same period. Nasopharyngeal swabs [n=142] were collected from patients with influenza and influenza-like illness. Typing and subtyping of the isolates were performed using multiplex RT-PCR and phylogenetic analysis was carried out for hemagglutinin genes of the isolates. Fifty out of 142 samples were positive for influenza A virus, and no influenza B virus was detected. Phylogenetic analyses revealed that the A/H1N1 isolates were related closely to A/Brisbane/59/2007, and the A/H3N2 isolates were close to A/Brisbane/10/2007 vaccine strains. The findings of the present study demonstrate that the A/H1N1 was the predominant subtype of human influenza virus among the patients studied in Tehran during 2008-2009 winter seasons. In addition, some amino acid variation was found in Tehran/2008/H1N1 isolates from the 2008-2009 vaccine strain, but the H3N2 isolates showed higher genetic resemblance to the vaccine strain