Hepatitis Delta Virus (HDV) infects only patients that are already infected by hepatitis B virus (HBV) because this is sub satellite virus which depends on and propagate only in the presence of HBV. HDV causes co-infection or super infection with sever complication as compared to only HBV infection. No study on molecular level on HDV is available from this region; therefore, the aim of this study was to found out the molecular epidemiology of HDV (as a co-infection with HBV) in different geographical regions of Pakistan.Total 228 HBsAg positive samples were received for the study from different geographical regions of the country. Only HBV DNA PCR positive samples were further utilized for the presence of HDV RNA. For this purpose, HDV RNA and HBV DNA was extracted and amplified using reverse transcriptase polymerase chain reaction (RT-PCR), nested PCR and real-time PCR.Out of the total 228 HBsAg positive samples, HBV DNA was detected in total 190 (83.3%) samples belonged to different patients. Of these 190 patients, HDV RNA was observed in 53 (28%) patients. Of the 53 HDV positive cases, 37 (69.8%) were males and 16 (30.2%) were female patients. The percentage of dual infection was found higher significantly (p < 0.05) in male patients as compared to female patients. Total 41 (26.8%) patients were below 40 years and 13 (31.7%) were above 40 years of age. No significant difference was seen in patients with ages above or below 40 years. In the provinces of Sindh, Khyber Pakhtoonkhaw and Punjab the observed prevalence of HDV was 67%, 6% and 4% respectively.In conclusion, the HDV infection is not uncommon in Pakistan and its prevalence is higher significantly in the Province of Sindh (p < 0.01) and male six (p < 0.05).
Development of new drugs is a time-taking and expensive process. Comprehensive efforts are being made globally toward the search of therapeutics against SARS-CoV-2. Several drugs such as remdesivir, favipiravir, ritonavir, and lopinavir have been included in the treatment regimen and shown effective results in several cases. Among the existing broad-spectrum antiviral drugs, remdesivir is found to be more effective against SARS-CoV-2. Remdesivir has broad-spectrum antiviral action against many single-stranded RNA viruses including pathogenic SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV). In this study, we proposed that remdesivir strongly binds to membrane protein (Mprotein), RNA-dependent RNA polymerase (RDRP), and main protease (Mprotease) of SARS-CoV-2. It might show antiviral activity by inhibiting more than one target. It has been found that remdesivir binds to Mprotease, Mprotein, and RDRP with −7.8, −7.4, and −7.1 kcal/mol, respectively. The structure dynamics study suggested that binding of remdesivir leads to unfolding of RDRP. It has been found that strong binding of remdesivir to Mprotein leads to decrease in structural deviations and gyrations. Additionally, the average solvent-accessible surface area of Mprotein decreases from 127.17 to 112.12 nm2, respectively. Furthermore, the eigenvalues and the trace of the covariance matrix were found to be low in case of Mprotease–remdesivir, Mprotein–remdesivir, and RDRP–remdesivir. Binding of remdesivir to Mprotease, Mprotein, and RDRP reduces the average motions in protein due to its strong binding. The MMPBSA calculations also suggested that remdesivir has strong binding affinity with Mprotein, Mprotease, and RDRP. The detailed analysis suggested that remdesivir has more than one target of SARS-CoV-2.
Objectives. To investigate the impact of an integrated care model on the health-related quality of life (HRQOL) of formerly chronically homeless individuals in permanent supportive housing. Methods. From 2014 to 2017, eligible individuals in Houston, Texas (n = 323), were placed in 1 of 2 permanent supportive housing service delivery models. Both models included coordinated care teams. In the intervention group, teams had a single plan of care with the partnering clinic. The 9-item Patient Health Questionnaire and 36-item Short Form Survey were administered at baseline and every 6 months for 30 months. We assessed intervention group emergency department use at 2 years. We evaluated change by using hierarchical linear growth models. Results. There was a significant and clinically meaningful increase in HRQOL in the intervention group, with the intervention group reporting improvement over the comparison group. Intervention group emergency department use decreased by 70% (no comparison group). Conclusions. Those in the intervention group with a single, coordinated plan of care reported significant and clinically meaningful increases in their HRQOL. Public Health Implications. Coordinated care models have potential to reduce societal costs and increase HRQOL, providing a financial and humanitarian justification for the continued investment in collaborative care in permanent supportive housing.
Background. Coronaviruses (CoVs) are enveloped positive-strand RNA viruses which have club-like spikes at the surface with a unique replication process. Coronaviruses are categorized as major pathogenic viruses causing a variety of diseases in birds and mammals including humans (lethal respiratory dysfunctions). Nowadays, a new strain of coronaviruses is identified and named as SARS-CoV-2. Multiple cases of SARS-CoV-2 attacks are being reported all over the world. SARS-CoV-2 showed high death rate; however, no specific treatment is available against SARS-CoV-2. Methods. In the current study, immunoinformatics approaches were employed to predict the antigenic epitopes against SARS-CoV-2 for the development of the coronavirus vaccine. Cytotoxic T-lymphocyte and B-cell epitopes were predicted for SARS-CoV-2 coronavirus protein. Multiple sequence alignment of three genomes (SARS-CoV, MERS-CoV, and SARS-CoV-2) was used to conserved binding domain analysis. Results. The docking complexes of 4 CTL epitopes with antigenic sites were analyzed followed by binding affinity and binding interaction analyses of top-ranked predicted peptides with MHC-I HLA molecule. The molecular docking (Food and Drug Regulatory Authority library) was performed, and four compounds exhibiting least binding energy were identified. The designed epitopes lead to the molecular docking against MHC-I, and interactional analyses of the selected docked complexes were investigated. In conclusion, four CTL epitopes (GTDLEGNFY, TVNVLAWLY, GSVGFNIDY, and QTFSVLACY) and four FDA-scrutinized compounds exhibited potential targets as peptide vaccines and potential biomolecules against deadly SARS-CoV-2, respectively. A multiepitope vaccine was also designed from different epitopes of coronavirus proteins joined by linkers and led by an adjuvant. Conclusion. Our investigations predicted epitopes and the reported molecules that may have the potential to inhibit the SARS-CoV-2 virus. These findings can be a step towards the development of a peptide-based vaccine or natural compound drug target against SARS-CoV-2.
Coronaviruses (CoVs) belong to the Coronaviridae-family. The genus Betacoronaviruses, are enveloped positive strand RNA viruses with club-like spikes at the surface with a unique replication process and a large RNA genome (∼25 kb). CoVs are known as one of the major pathogenic viruses causing a variety of diseases in birds and mammals including humans (lethal respiratory dysfunctions). Recently, a new strain of coronavirus has been identified and named as SARS-CoV-2. A large number of COVID-19 (disease caused by SARS-CoV-2) cases are being diagnosed all over the World especially in China (Wuhan). COVID-19 showed high mortality rate exponentially, however, not even a single effective cure is being introduced yet against COVID-19. In the current study, immunoinformatics approaches were employed to predict the antigenic epitopes against COVID-19 for the development of a coronavirus peptide vaccine. Cytotoxic T-lymphocyte (CTL) and B-cell epitopes were predicted for SARS-CoV-2 coronavirus structural proteins (Spikes, Membrane, Envelope, and Nucleocapsid). The docking complexes of the top 10 epitopes having antigenic sites were analyzed led by binding affinity and binding interactional analyses of top ranked predicted peptides with the MHC-I HLA molecule. The predicted peptides may have potential to be used as peptide vaccine against COVID-19.
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