Although vaccination is used to control HBV among prisoners, prevalence of HCV exposure is alarming in the prison population of Iran, especially among people who inject drugs. Eliminating viral hepatitis in Iran by 2030 requires a national commitment and rapid measures for targeting this high-risk group. Given the increased efficiency of HCV treatment in recent years, prisons provide an opportunity to access patients for treatment.
The causative agent of severe acute respiratory syndrome (SARS) reported by the Chinese Center for Disease Control (China CDC) has been identified as a novel Betacoronavirus (SARS-CoV-2). A computational approach was adopted to identify multiepitope vaccine candidates against SARS-CoV-2 based on S, N and M proteins being able to elicit both humoral and cellular immune responses. In this study, the sequence of the virus was obtained from NCBI database and analyzed with in silico tools such as NetMHCpan, IEDB, BepiPred, NetCTL, Tap transport/proteasomal cleavage, Pa 3 P, GalexyPepDock, I-TASSER, Ellipro and ClusPro. To identify the most immunodominant regions, after analysis of population coverage and epitope conservancy, we proposed three different constructs based on linear B-cell, CTL and HTL epitopes. The 3D structure of constructs was assessed to find discontinuous B-cell epitopes. Among CTL predicted epitopes, S 257-265 , S 603-611 and S 360-368 , and among HTL predicted epitopes, N 167-181 , S 313-330 and S 1110-1126 had better MHC binding rank. We found one putative CTL epitope, S 360-368 related to receptor-binding domain (RBD) region for S protein. The predicted epitopes were non-allergen and showed a high quality of proteasomal cleavage and Tap transport efficiency and 100% conservancy within four different clades of SARS-CoV-2. For CTL and HTL epitopes, the highest population coverage of the world’s population was calculated for S 27-37 with 86.27% and for S 196-231 , S 303-323 , S 313-330 , S 1009-1030 and N 328-349 with 90.33%, respectively. We identified overall 10 discontinuous B-cell epitopes for three multiepitope constructs. All three constructs showed strong interactions with TLRs 2, 3 and 4 supporting the hypothesis of SARS-CoV-2 susceptibility to TLRs 2, 3 and 4 like other Coronaviridae families. These data demonstrated that the novel designed multiepitope constructs can contribute to develop SARS-CoV-2 peptide vaccine candidates. The in vivo studies are underway using several vaccination strategies.
Background: Despite the progress in the discovery of antiretroviral compounds for treating HIV-1 infection by targeting HIV integrase (IN), a promising and well-known drug target against HIV-1, there is a growing need to increase the armamentarium against HIV, for avoiding the drug resistance issue. Objective: To develop novel HIV-1 IN inhibitors, a series of 3-hydroxy-pyrane-4-one (HP) and 3- hydroxy-pyridine-4-one (HPO) derivatives have been rationally designed and synthesized. Methods: To provide a significant characterization of the novel compounds, in-depth computational analysis was performed using a novel HIV-1 IN/DNA binary 3D-model for investigating the binding mode of the newly conceived molecules in complex with IN. The 3D-model was generated using the proto-type foamy virus (PFV) DNA as a structural template, positioning the viral polydesoxyribonucleic chain into the HIV-1 IN homology model. Moreover, a series of in vitro tests were performed including HIV-1 activity inhibition, HIV-1 IN activity inhibition, HIV-1 IN strand transfer activity inhibition and cellular toxicity. Results: Bioassay results indicated that most of HP analogues including HPa, HPb, HPc, HPd, HPe and HPg, showed favorable inhibitory activities against HIV-1-IN in the low micromolar range. Particularly halogenated derivatives (HPb and HPd) offered the best biological activities in terms of reduced toxicity and optimum inhibitory activities against HIV-1 IN and HIV-1 in cell culture. Conclusion: Halogenated derivatives, HPb and HPd, displayed the most promising anti-HIV profile, paving the way to the optimization of the presented scaffolds for developing new effective antiviral agents.
Background: People in prisons are at high risk of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. Objectives: This study aimed to evaluate the prevalence of HBV and HCV exposure and associated risk factors in Iranian prisons. Methods: This cross-sectional study was conducted in 2016, among 29 prisons in Iran, blood samples were collected using multistage sampling. HBV and HCV diagnostic tests were conducted using enzyme-linked immunosorbent assay (ELISA). Univariate and multivariate logistic regression were used for the evaluation of factors associated with HBV and HCV exposure. Results: Among 6,481 people in prisons, the prevalence of HCV and HBV antibodies were 8.21% (95% CI: 7.55 -8.90) and 3.06% (95% CI: 2.65 -3.50), respectively. Based on multivariate analysis, the most important risks associated for HCV exposure were the history of drug use (AOR 5.75, 95% CI 3.54 -9.35) followed by the age of 30 years and older (AOR: 5.02, 95% CI: 3.65 -6.9), the history of tattooing (AOR 2.42, 95% CI 1.96 -3), the history of imprisonment (AOR 2.23, 95%CI 1.76 -2.82), being single (AOR 1.91, 95% CI 1.54 -2.37), low education (AOR 1.81, 95%CI 1.01 -3.27), and the history of piercing (AOR 1.26, 95% CI 1.04 -1.52). There was no significant association between HBV prevalence and independent variables (P > 0.05). Conclusions: These findings highlight a high prevalence of HCV infection in Iranian prisons. Efforts are needed to improve HCV screening and interventions, particularly among people with a history of drug use, and linkage to care.
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