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  1. Article ; Online: Analysis of temporal changes in HIV-1 CRF01_AE gag genetic variability and CD8 T-cell epitope evolution

    Wardah Rafaqat / Uroosa Tariq / Nida Farooqui / Maheen Zaidi / Aanish Raees / Maaz Zuberi / Amna Batool / Syed Hani Abidi

    PLoS ONE, Vol 17, Iss

    2022  Volume 5

    Abstract: Currently, little is known about the time-dependent evolution of human immunodeficiency virus-1 (HIV-1) circulating recombinant forms (CRF) 01_AE, a dominant recombinant form associated with HIV-1 epidemics worldwide. Since gag is a highly immunodominant ...

    Abstract Currently, little is known about the time-dependent evolution of human immunodeficiency virus-1 (HIV-1) circulating recombinant forms (CRF) 01_AE, a dominant recombinant form associated with HIV-1 epidemics worldwide. Since gag is a highly immunodominant HIV-1 protein, we performed a comparative analysis of the CRF01_AE gag protein’s time-dependent changes and evolution. A total of 3105 HIV-1 CRF01_AE gag sequences representing 17 countries from the timeline 1990–2017 were obtained. The sequences’ phylogenetic relationship and epidemic dynamics were analyzed through a Maximum Likelihood tree and Bayesian Skyline plot, respectively. Genomic variability was measured through Shannon entropy and time-dependent immunoevolution was analyzed using changes in proteasomal degradation pattern, cytotoxic T lymphocytes (CTL) epitopes, and Human leukocyte antigens (HLA) restriction profile. The most recent common ancestor of the HIV CRF01_AE epidemic was estimated to be 1974±1. A period of exponential growth in effective population size began in 1982, fluctuated, and then stabilized in 1999. Genetic variability (entropy) consistently increased, however, epitope variability remained comparable; the highest number of novel CTL epitopes were present in 1995–1999, which were lost over time. The spread of the HIV-1 CRF01_AE epidemic is predominant in countries within Asia. Population immunogenetic pressures in the region may have contributed to the initial changes and following adaptation/stabilization of epitope diversity within gag sequences.
    Keywords Medicine ; R ; Science ; Q
    Subject code 570
    Language English
    Publishing date 2022-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Analysis of temporal changes in HIV-1 CRF01_AE gag genetic variability and CD8 T-cell epitope evolution.

    Wardah Rafaqat / Uroosa Tariq / Nida Farooqui / Maheen Zaidi / Aanish Raees / Maaz Zuberi / Amna Batool / Syed Hani Abidi

    PLoS ONE, Vol 17, Iss 5, p e

    2022  Volume 0267130

    Abstract: Currently, little is known about the time-dependent evolution of human immunodeficiency virus-1 (HIV-1) circulating recombinant forms (CRF) 01_AE, a dominant recombinant form associated with HIV-1 epidemics worldwide. Since gag is a highly immunodominant ...

    Abstract Currently, little is known about the time-dependent evolution of human immunodeficiency virus-1 (HIV-1) circulating recombinant forms (CRF) 01_AE, a dominant recombinant form associated with HIV-1 epidemics worldwide. Since gag is a highly immunodominant HIV-1 protein, we performed a comparative analysis of the CRF01_AE gag protein's time-dependent changes and evolution. A total of 3105 HIV-1 CRF01_AE gag sequences representing 17 countries from the timeline 1990-2017 were obtained. The sequences' phylogenetic relationship and epidemic dynamics were analyzed through a Maximum Likelihood tree and Bayesian Skyline plot, respectively. Genomic variability was measured through Shannon entropy and time-dependent immunoevolution was analyzed using changes in proteasomal degradation pattern, cytotoxic T lymphocytes (CTL) epitopes, and Human leukocyte antigens (HLA) restriction profile. The most recent common ancestor of the HIV CRF01_AE epidemic was estimated to be 1974±1. A period of exponential growth in effective population size began in 1982, fluctuated, and then stabilized in 1999. Genetic variability (entropy) consistently increased, however, epitope variability remained comparable; the highest number of novel CTL epitopes were present in 1995-1999, which were lost over time. The spread of the HIV-1 CRF01_AE epidemic is predominant in countries within Asia. Population immunogenetic pressures in the region may have contributed to the initial changes and following adaptation/stabilization of epitope diversity within gag sequences.
    Keywords Medicine ; R ; Science ; Q
    Subject code 570
    Language English
    Publishing date 2022-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Impact of Perfectionism and Resilience on Empathy in Medical Students

    Wardah Rafaqat / Ashmal Sami / Muhammad Talal Ibrahim / Hamza Ibad / Sheharbano Awais / Ayesha Memon / Fatima Farrukh Shahbaz / Daniyaal Ahmed / Shahzaib Zindani / Abdul Lateef Leghari / Sarah Saleem

    Journal of Patient Experience, Vol

    A Cross-Sectional Study

    2022  Volume 9

    Abstract: Empathy is a cognitive attribute that forms the cornerstone for good doctor–patient encounters. The formative period for the development of empathy toward patients begins with clinical encounters within medical school. An individual medical student's ... ...

    Abstract Empathy is a cognitive attribute that forms the cornerstone for good doctor–patient encounters. The formative period for the development of empathy toward patients begins with clinical encounters within medical school. An individual medical student's empathy levels may in part be a product of their resilience and perfectionist attitudes. A cross-sectional study with 320 medical students across all years of study was conducted to determine the correlation of perfectionism and resilience with clinical empathy in medical students. The JSE-S, CD-RISC 10, and APS-R scales were used to assess levels of empathy, resilience, and perfectionism, respectively. The study found that a positive correlation exists between resilience ( r = 0.174) and academic year with empathy, and a negative correlation exists between maladaptive perfectionism and empathy ( r = −0.138). The resilience score declined progressively as the year of study progressed with a statistically significant. Mean empathy scores were lowest in fifth-year students (96.8 ± 12.5) and highest in third-year students (107.8 ± 13.2). Further longitudinal studies are necessary to better understand the impact of resilience and perfectionism on empathy.
    Keywords Medicine (General) ; R5-920
    Language English
    Publishing date 2022-06-01T00:00:00Z
    Publisher SAGE Publishing
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Repurposing potential of posaconazole and grazoprevir as inhibitors of SARS-CoV-2 helicase

    Syed Hani Abidi / Nahlah Makki Almansour / Daulet Amerzhanov / Khaled S. Allemailem / Wardah Rafaqat / Mahmoud A. A. Ibrahim / Philip la Fleur / Martin Lukac / Syed Ali

    Scientific Reports, Vol 11, Iss 1, Pp 1-

    2021  Volume 11

    Abstract: Abstract As the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) pandemic engulfs millions worldwide, the quest for vaccines or drugs against the virus continues. The helicase protein of SARS-CoV-2 represents an attractive target for drug ... ...

    Abstract Abstract As the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) pandemic engulfs millions worldwide, the quest for vaccines or drugs against the virus continues. The helicase protein of SARS-CoV-2 represents an attractive target for drug discovery since inhibition of helicase activity can suppress viral replication. Using in silico approaches, we have identified drugs that interact with SARS-CoV-2 helicase based on the presence of amino acid arrangements matching binding sites of drugs in previously annotated protein structures. The drugs exhibiting an RMSD of ≤ 3.0 Å were further analyzed using molecular docking, molecular dynamics (MD) simulation, and post-MD analyses. Using these approaches, we found 12 drugs that showed strong interactions with SARS-CoV-2 helicase amino acids. The analyses were performed using the recently available SARS-CoV-2 helicase structure (PDB ID: 5RL6). Based on the MM-GBSA approach, out of the 12 drugs, two drugs, namely posaconazole and grazoprevir, showed the most favorable binding energy, − 54.8 and − 49.1 kcal/mol, respectively. Furthermore, of the amino acids found conserved among all human coronaviruses, 10/11 and 10/12 were targeted by, respectively, grazoprevir and posaconazole. These residues are part of the crucial DEAD-like helicase C and DEXXQc_Upf1-like/ DEAD-like helicase domains. Strong interactions of posaconazole and grazoprevir with conserved amino acids indicate that the drugs can be potent against SARS-CoV-2. Since the amino acids are conserved among the human coronaviruses, the virus is unlikely to develop resistance mutations against these drugs. Since these drugs are already in use, they may be immediately repurposed for SARS-CoV-2 therapy.
    Keywords Medicine ; R ; Science ; Q
    Subject code 572
    Language English
    Publishing date 2021-05-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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