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Graves Rios posted an update 5 days ago
Human immunodeficiency virus (HIV) is a pathogen that infects blood cells, using CD4 molecule and two cell receptors CCR5 and CXCR4. The other major actor is gp120/gp41 viral protein complex, which interacts with receptors. Here, the presence of synonymous mutations associated with HIV-1 tropism and the related RNA secondary-structure in HIV-1 infected patients was evaluated. The analysis includes gp120-sequences from 340 HIV-1 subtype-B infected patients, all retrieved from Los Alamos database and with phenotypic HIV tropism determination based on recombinant-virus entry-assay. Frequencies of all nucleotide substitutions were calculated. Mfold and RNAfold algorithms were used to predict RNA secondary-structure of HIV-1. Nineteen codons in V2/C2, V3 and C3 domains were found to be closely related to CCR5 and CXCR4. Additionally, in X4-sequences, gp120 gca303gcu and gua222guc synonymous mutations are positively related to the gp120 S11R and T8A/I codons in V3 protein domain. Furthermore, gua222guc increases stability of the viral RNA secondary-structure. Probably, it would not be surprising if a novel escape viral strategy therapy will be related to the gp120 synonymous mutations. Moreover, in relation to the pivotal role played by gp120 in polyvalent vaccine approaches, the impact of gp120 synonymous mutations may play an important role in HIV entry into the cell. Keywords gp120; tropism; v3; s11r; evolution; vaccine.The deadly disease-causing novel coronavirus has recently swept across the world and endangered many human lives. Although, various research on therapeutic measures to solve this pandemic crisis has been published; no favourable results have been achieved. We propose the use of potential FDA-approved dual inhibitors which can inhibit two targets (either on entry-level or the main protease) for the effective treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). BMS303141 We screened 12 FDA-approved antiviral inhibitors listed in Drug bank and analysed the ADMET properties of each drug of interest to study the bioavailability, safety and toxicity. Two potential targets, the spike protein and the main protease of SARS-CoV-2 obtained from PDB have been used for molecular docking. All the selected drugs were docked with both targets and demonstrated strong hydrogen bond (HB) interactions in multiple active sites. Amongst these, the range of binding energy was from 3-7 kcal/mol for spike protein and 2-8 kcal/mol for the main protease. Upon comparison of all the processed drugs ganciclovir and zanamivir displayed significant binding energy with HB interactions with both, spike (-9.2 and -9 kcal/mol respectively) and the main protease (-9 kcal/mol). Ribavirin and tenofovir showed significant binding energy above -8 kcal/mol with seven HB interactions with the main protease and also spike protein. The novel findings regarding the antiviral properties of these dual inhibitors using a computational approach will be a good starting point for the efficacy determination of these drugs for pre-clinical and clinical studies aimed at developing active antivirals to target SARS-CoV-2. Keywords SARS-CoV-2; FDA-approved drugs; viral inhibitors; in-silico analysis; molecular docking.Circulation of dominant genotype VII of Newcastle disease virus (NDV) causes significant economic losses to the poultry industry in China. Although most of genotype VII NDV has frequently been isolated in China to date, the genome sequence difference between duck-origin and chicken-origin NDVs remains largely unknown. In this study, a NDV strain of Chicken/China/HB/2017 (HB), isolated during an outbreak in China, was subjected to genetic, biological, phylogenetic and the pathogenicity characterization. The complete genome of HB strain is 15,192 nucleotides (nt) long and consisting of six genes in the order of 3′-NP-P-M-F-HN-L-5′. Several amino acid mutations were identified in the functional domains of F and HN proteins, including fusion peptide, heptad repeat region, transmembrane domains, and neutralizing epitopes. Phylogenetic analysis based on the F gene revealed that the HB strain and three other duck-origin NDV strains in China were grouped under subgenotype VII.1.1 and shared 99.1~99.2% nucleotide identity. Additionally, the challenge experiment results showed that the strain was highly pathogenic with 100% morbidity and mortality. Virus shedding was detected from 2 days post-infection until the fifth day. In conclusion, this study offers our understanding of circulating strains of NDV and genes involved in virulence and evolution between different hosts. Keywords Newcastle disease virus; China; complete genome; genotype VII; mutations.Direct acting antiviral agents (DAAs) are a group of antiviral drugs that inhibit specific non-structural proteins of the virus and disrupt viral replication and infection. DAAs regimens for hepatitis C virus (HCV) infection provide a particular event to tackle mechanistic intracellular relationships between the innate immunity and HCV, potentially providing perceptions about the rate of the viral replication and complex decay. Interleukin 29 (IL-29) prevents the replication of HCV. IFN-inducible protein 10 (IP-10) plays a significant role in the pathogenesis of HCV infection. MIG/CXCL9 are produced by inflammatory and stromal cells such as hepatocytes following either stimulation by interferon lambda (IFNγ) or viral infection. This study aimed to evaluate the co-expression of IL-29, IP-10 and MIG in peripheral blood mononuclear cells (PBMCs) from untreated and treated chronic HCV patients with DAAs. This study included group of twenty naïve HCV patients, group of twenty sustained viral response (SVR) patients and a control group that consisted of 10 healthy subjects. All subjects were tested for liver enzymes, serum albumin level, total serum bilirubin, platelet count, prothrombin activity and viral load. Relative gene expression of IL-29, IP-10, and MIG in PBMCs from all subjects was determined using real time PCR. The mean value of IL-29, IP-10 and MIG gene expression significantly increased in both naïve HCV and SVR groups of patients as compared to normal subjects. The corresponding value was significantly lower in patients with SVR compared to naïve HCV patients. Infection with HCV significantly trigged the co-expression of IL-29, IP-10, and CXCL9 (MIG) genes in PBMCs of chronic hepatitis C patients and significantly down-regulated in those who achieved SVR after successful DAAs therapy. Keywords IP10; MIG; IL29; HCV; DAAs; gene expression.