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22 results on '"Alamer, Edrous"'

5. Structure-guided drug design identifies a BRD4-selective small molecule that suppresses HIV

Author

Niu, Qingli, Liu, Zhiqing, Alamer, Edrous, Fan, Xiuzhen, Chen, Haiying, Endsley, Janice, Gelman, Benjamin B., Tian, Bing, Kim, Jerome H., Michael, Nelson L., Robb, Merlin L., Ananworanich, Jintanat, Zhou, Jia, and Hu, Haitao

Subjects
Control, Drug therapy, Analysis, Health aspects, Epigenetic inheritance -- Analysis -- Health aspects, Efavirenz -- Analysis -- Health aspects, Protein binding -- Analysis -- Health aspects, Highly active antiretroviral therapy -- Analysis -- Health aspects, Raltegravir -- Analysis -- Health aspects, HIV -- Drug therapy -- Analysis -- Control -- Health aspects, Virus diseases -- Drug therapy -- Analysis -- Control -- Health aspects, Infection -- Drug therapy -- Analysis -- Health aspects, Genomes -- Analysis -- Health aspects, Proteins -- Analysis -- Health aspects, Antiretroviral agents, Genomics, Chromatin, Viremia
Abstract

Introduction HIV infection continues to cause a global pandemic. Antiretroviral therapy (ART) can effectively suppress active HIV replication and has improved survival and quality of life of HIV-infected individuals. However, [...], HIV integrates its provirus into the host genome and establishes latent infection. Antiretroviral therapy (ART) can control HIV viremia, but cannot eradicate or cure the virus. Approaches targeting host epigenetic machinery to repress HIV, leading to an aviremic state free of ART, are needed. Bromodomain and extraterminal (BET) family protein BRD4 is an epigenetic reader involved in HIV transcriptional regulation. Using structure-guided drug design, we identified a small molecule (ZL0580) that induced epigenetic suppression of HIV via BRD4. We showed that ZL0580 induced HIV suppression in multiple in vitro and ex vivo cell models. Combination treatment of cells of aviremic HIV-infected individuals with ART and ZL0580 revealed that ZL0580 accelerated HIV suppression during ART and delayed viral rebound after ART cessation. Mechanistically different from the BET/BRD4 pan-inhibitor JQ1, which nonselectively binds to BD1 and BD2 domains of all BET proteins, ZL0580 selectively bound to BD1 domain of BRD4. We further demonstrate that ZL0580 induced HIV suppression by inhibiting Tat transactivation and transcription elongation as well as by inducing repressive chromatin structure at the HIV promoter. Our findings establish a proof of concept for modulation of BRD4 to epigenetically suppress HIV and provide a promising chemical scaffold for the development of probes and/or therapeutic agents for HIV epigenetic silencing.

Published
2019
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15. Low clinical utility of testing for anti‐platelet factor 4 in asymptomatic individuals after ChAdOx1 nCoV‐19 vaccine

Author

Barefah, Ahmed S., primary, Radhwi, Osman O., additional, Alamri, Sawsan S., additional, Alahwal, Hatem M., additional, Denetiu, Iuliana, additional, Almohammadi, Abdullah T., additional, Bahashwan, Salem M., additional, Qari, Mohamad H., additional, Algaissi, Abdullah, additional, Alamer, Edrous, additional, Alhazmi, Abdulaziz, additional, Abuzenadah, Adel M., additional, Nasraldeen, Walleed H., additional, Alzahrani, Sami H., additional, and Hashem, Anwar M., additional

Published
2021
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18. Knowledge, Attitudes and Perception toward COVID-19 Vaccines among Adults in Jazan Province, Saudi Arabia

Author

Alamer, Edrous, primary, Hakami, Faisal, additional, Hamdi, Sulaiman, additional, Alamer, Afnan, additional, Awaf, Mohammed, additional, Darraj, Hussam, additional, Abutalib, Yumna, additional, Madkhali, Ebtisam, additional, Alamer, Rahaf, additional, Bakri, Nawaf, additional, Qadri, Marwa, additional, Algaissi, Abdullah, additional, and Alhazmi, Abdulaziz, additional

Published
2021
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20. IL-22 hinders antiviral T cell responses and exacerbates neurological disorders in ZIKV-infected immunocompetent neonatal mice

Author

Liang, Yuejin, primary, Yi, Panpan, additional, Ru, Wenjuan, additional, Jie, Zuliang, additional, Wang, Hui, additional, Ghanayem, Tamer, additional, Wang, Xiaofang, additional, Alamer, Edrous, additional, Liu, Jinjun, additional, Hu, Haitao, additional, Soong, Lynn, additional, Cai, Jiyang, additional, and Sun, Jiaren, additional

Published
2020
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22. Low clinical utility of testing for anti‐platelet factor 4 in asymptomatic individuals after ChAdOx1 nCoV‐19 vaccine.

Author

Barefah, Ahmed S., Radhwi, Osman O., Alamri, Sawsan S., Alahwal, Hatem M., Denetiu, Iuliana, Almohammadi, Abdullah T., Bahashwan, Salem M., Qari, Mohamad H., Algaissi, Abdullah, Alamer, Edrous, Alhazmi, Abdulaziz, Abuzenadah, Adel M., Nasraldeen, Walleed H., Alzahrani, Sami H., and Hashem, Anwar M.

Subjects
COVID-19 vaccines, MEDICAL care use, PRE-tests & post-tests, PLATELET aggregation inhibitors, ENZYME-linked immunosorbent assay, DESCRIPTIVE statistics, COVID-19 testing, LONGITUDINAL method
Abstract

Introduction: The development of anti‐platelet factor 4 (PF4) antibodies is linked to a rare thrombotic complication described now as vaccine‐induced immune thrombotic thrombocytopenia (VITT). This clinical syndrome with thrombosis and thrombocytopenia was reported after exposure to the Oxford‐AstraZeneca COVID‐19 vaccine, ChAdOx1 nCoV‐19 vaccine (AZD1222), and Ad26.COV2.S vaccine (Janssen/Johnson & Johnson). In the absence of the clinical features, the incidence of positive anti‐PF4 antibodies in asymptomatic individuals post‐vaccination is unclear. Methods: The aim of this study was to evaluate the development of anti‐PF4 antibodies in asymptomatic individuals 14–21 days after receiving the first dose of ChAdOx1 nCoV‐19 vaccine (AZD1222) and BNT162b2 vaccine. Prospectively, we collected serum from individuals before and after ChAdOx1 nCoV‐19 vaccine and BNT162b2 vaccine and measured anti‐PF4 antibodies using the Asserachrom HPIA IgG ELISA (Stago, Asnieres, France). Results: We detected positive anti‐PF4 antibodies in 5 of 94 asymptomatic individuals post‐vaccine with a rate of 5.3% with low titers (OD 0.3–0.7). Four of 5 individuals who tested positive after the vaccine had also positive anti‐PF4 antibodies before the vaccine, which indicates that a majority of the positive results are due to preexisting anti‐PF4 antibodies. We did not find a relation between the development of anti‐PF4 antibodies and the immune response to the vaccine, status of prior COVID‐19 infection, and baseline characteristics of participants. None of the participants developed thrombosis nor thrombocytopenia. Conclusion: Our results provide new evidence to guide the diagnostic algorithm of suspected cases of VITT. In the absence of thrombosis and thrombocytopenia, there is a low utility of testing for anti‐PF4 antibodies. [ABSTRACT FROM AUTHOR]

Published
2022
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