摘要 :
Broadly neutralizing antibodies (bNAbs) are potent in neutralizing a wide range of HIV strains. VRC01 is a CD4-binding-site (CD4-bs) class of bNAbs that binds to the conserved CD4-binding region of HIV-1 envelope (env) protein. Na...
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Broadly neutralizing antibodies (bNAbs) are potent in neutralizing a wide range of HIV strains. VRC01 is a CD4-binding-site (CD4-bs) class of bNAbs that binds to the conserved CD4-binding region of HIV-1 envelope (env) protein. Natural products that mimic VRC01 bNAbs by interacting with the conserved CD4-binding regions may serve as a new generation of HIV-1 entry inhibitors by being broadly reactive and potently neutralizing. This study aimed to identify compounds that mimic VRC01 by interacting with the CD4-bs of HIV-1 gp120 and thereby inhibiting viral entry into target cells. Libraries of purchasable natural products were virtually screened against clade A/E recombinant 93TH057 (PDB: 3NGB) and clade B (PDB ID: 3J70) HIV-1 env protein. Protein–ligand interaction profiling from molecular docking and dynamics simulations showed that the compounds had intermolecular hydrogen and hydrophobic interactions with conserved amino acid residues on the CD4-binding site of recombinant clade A/E and clade B HIV-1 gp120. Four potential lead compounds, NP-005114, NP-008297, NP-007422, and NP-007382, were used for cell-based antiviral infectivity inhibition assay using clade B (HXB2) env pseudotype virus (PV). The four compounds inhibited the entry of HIV HXB2 pseudotype viruses into target cells at 50% inhibitory concentrations (IC50) of 15.2 μM (9.7 μg/mL), 10.1 μM (7.5 μg/mL), 16.2 μM (12.7 μg/mL), and 21.6 μM (12.9 μg/mL), respectively. The interaction of these compounds with critical residues of the CD4-binding site of more than one clade of HIV gp120 and inhibition of HIV-1 entry into the target cell demonstrate the possibility of a new class of HIV entry inhibitors.
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In Ghana, majority of cancer studies have focused on only two main teaching hospitals. However, there is the need to study the disease burden from other parts of the country. This study was designed to review cancer cases recorded...
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In Ghana, majority of cancer studies have focused on only two main teaching hospitals. However, there is the need to study the disease burden from other parts of the country. This study was designed to review cancer cases recorded in major hospitals in the Volta Region of Ghana, with the aim of determining the incidence of cancers and cancer-related mortalities, and contribute to cancer data in the country. In-patient diagnosis data from 2012 to 2014 were collected from 21 hospitals in the Volta Region of Ghana. The data were entered and structured in Microsoft Excel and analyzed with IBM SPSS Statistics 20 and GraphPad Prism 6. Cervical, breast, liver, soft tissue, and prostate cancer were identified as the commonly diagnosed cancers in the Region. Socioeconomic factors such as poor educational background and occupation were associated with incidence of cancer in the study area. The incidence of cancer was determined to be approximately 9, 11, and 6 morbidities per 100,000 people in the years 2012, 2013, and 2014, respectively, with liver cancer being the leading cause of deaths. Public awareness and screening efforts are thus needed to fight against cancer in the Volta Region, and Ghana as a whole. In addition, this study is an original report of cancers in the Volta Region of Ghana and underscores the need to report ethnic/population-specific frequencies to effectively evaluate the burden of cancer in the country.
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摘要 :
Over 40 filovirus disease outbreaks have been reported since the discovery of the first member of the Filoviridae family, and most of the outbreaks have occurred in Africa. In addition to deaths (primary impacts), there have also ...
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Over 40 filovirus disease outbreaks have been reported since the discovery of the first member of the Filoviridae family, and most of the outbreaks have occurred in Africa. In addition to deaths (primary impacts), there have also been health, social, economic, and political effects (secondary impacts) due to the outbreaks. Two large filovirus disease outbreaks have occurred in West and Central Africa in recent times, and direct and indirect repercussions resulting from the outbreaks underscores the need to strengthen the capacity of health services in disease hotspots.
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