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  1. Article ; Online: Integrase inhibitors: current protagonists in antiretroviral therapy.

    Loaiza, John D / Chvatal-Medina, Mateo / Hernandez, Juan C / Rugeles, Maria T

    Immunotherapy

    2023  Volume 15, Issue 17, Page(s) 1477–1495

    Abstract: Since HIV was identified as the etiological agent of AIDS, there have been significant advances in antiretroviral therapy (ART) that has reduced morbidity/mortality. Still, the viral genome's high mutation rate, suboptimal ART regimens, incomplete ... ...

    Abstract Since HIV was identified as the etiological agent of AIDS, there have been significant advances in antiretroviral therapy (ART) that has reduced morbidity/mortality. Still, the viral genome's high mutation rate, suboptimal ART regimens, incomplete adherence to therapy and poor control of the viral load generate variants resistant to multiple drugs. Licensing over 30 anti-HIV drugs worldwide, including integrase inhibitors, has marked a milestone since they are potent and well-tolerated drugs. In addition, they favor a faster recovery of CD4
    MeSH term(s) Humans ; Anti-HIV Agents/pharmacology ; Anti-HIV Agents/therapeutic use ; Integrase Inhibitors/therapeutic use ; HIV Infections/drug therapy
    Chemical Substances Anti-HIV Agents ; Integrase Inhibitors
    Language English
    Publishing date 2023-10-12
    Publishing country England
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 2495964-9
    ISSN 1750-7448 ; 1750-743X
    ISSN (online) 1750-7448
    ISSN 1750-743X
    DOI 10.2217/imt-2023-0011
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Molecular mechanisms by which the HIV-1 latent reservoir is established and therapeutic strategies for its elimination.

    Chvatal-Medina, Mateo / Lopez-Guzman, Carolina / Diaz, Francisco J / Gallego, Salomon / Rugeles, Maria T / Taborda, Natalia A

    Archives of virology

    2023  Volume 168, Issue 8, Page(s) 218

    Abstract: The human immunodeficiency virus type 1 (HIV-1) reservoir, composed of cells harboring the latent, integrated virus, is not eliminated by antiretroviral therapy. It therefore represents a significant barrier to curing the infection. The biology of HIV-1 ... ...

    Abstract The human immunodeficiency virus type 1 (HIV-1) reservoir, composed of cells harboring the latent, integrated virus, is not eliminated by antiretroviral therapy. It therefore represents a significant barrier to curing the infection. The biology of HIV-1 reservoirs, the mechanisms of their persistence, and effective strategies for their eradication are not entirely understood. Here, we review the molecular mechanisms by which HIV-1 reservoirs develop, the cells and compartments where the latent virus resides, and advancements in curative therapeutic strategies. We first introduce statistics and relevant data on HIV-1 infection, aspects of pathogenesis, the role of antiretroviral therapy, and the general features of the latent HIV reservoir. Then, the article is built on three main pillars: The molecular mechanisms related to latency, the different strategies for targeting the reservoir to obtain a cure, and the current progress in immunotherapy to counteract said reservoirs.
    MeSH term(s) Humans ; HIV-1/genetics ; HIV Infections/drug therapy ; Virus Latency ; CD4-Positive T-Lymphocytes ; Virus Replication
    Language English
    Publishing date 2023-08-02
    Publishing country Austria
    Document type Journal Article ; Review
    ZDB-ID 7491-3
    ISSN 1432-8798 ; 0304-8608
    ISSN (online) 1432-8798
    ISSN 0304-8608
    DOI 10.1007/s00705-023-05800-y
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Antibody Responses in COVID-19: A Review.

    Chvatal-Medina, Mateo / Mendez-Cortina, Yorjagis / Patiño, Pablo J / Velilla, Paula A / Rugeles, Maria T

    Frontiers in immunology

    2021  Volume 12, Page(s) 633184

    Abstract: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to spread worldwide as a severe pandemic. Although its seroprevalence is highly variable among territories, it has been reported at around 10%, but higher in health workers. ... ...

    Abstract The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to spread worldwide as a severe pandemic. Although its seroprevalence is highly variable among territories, it has been reported at around 10%, but higher in health workers. Evidence regarding cross-neutralizing response between SARS-CoV and SARS-CoV-2 is still controversial. However, other previous coronaviruses may interfere with SARS-CoV-2 infection, since they are phylogenetically related and share the same target receptor. Further, the seroconversion of IgM and IgG occurs at around 12 days post onset of symptoms and most patients have neutralizing titers on days 14-20, with great titer variability. Neutralizing antibodies correlate positively with age, male sex, and severity of the disease. Moreover, the use of convalescent plasma has shown controversial results in terms of safety and efficacy, and due to the variable immune response among individuals, measuring antibody titers before transfusion is mostly required. Similarly, cellular immunity seems to be crucial in the resolution of the infection, as SARS-CoV-2-specific CD4+ and CD8+ T cells circulate to some extent in recovered patients. Of note, the duration of the antibody response has not been well established yet.
    MeSH term(s) Antibodies, Neutralizing/blood ; Antibodies, Viral/blood ; CD4-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/immunology ; COVID-19/immunology ; COVID-19/therapy ; Female ; Humans ; Immunization, Passive/methods ; Immunoglobulin G/blood ; Immunoglobulin M/blood ; Male ; Severe acute respiratory syndrome-related coronavirus/immunology ; SARS-CoV-2/immunology ; Seroconversion ; Seroepidemiologic Studies ; Severity of Illness Index ; COVID-19 Serotherapy
    Chemical Substances Antibodies, Neutralizing ; Antibodies, Viral ; Immunoglobulin G ; Immunoglobulin M
    Language English
    Publishing date 2021-04-15
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2021.633184
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Humoral Response to BNT162b2 Vaccine Against SARS-CoV-2 Variants Decays After Six Months.

    Lopera, Tulio J / Chvatal-Medina, Mateo / Flórez-Álvarez, Lizdany / Zapata-Cardona, Maria I / Taborda, Natalia A / Rugeles, Maria T / Hernandez, Juan C

    Frontiers in immunology

    2022  Volume 13, Page(s) 879036

    Abstract: SARS-CoV-2 vaccines have shown very high effectiveness in real-world scenarios. However, there is compelling evidence for a fast-paced waning of immunity. The increasing number of new variants that could alter the severity, transmissibility, and ... ...

    Abstract SARS-CoV-2 vaccines have shown very high effectiveness in real-world scenarios. However, there is compelling evidence for a fast-paced waning of immunity. The increasing number of new variants that could alter the severity, transmissibility, and potential to evade the immune response raised significant concern. Therefore, elucidating changes in the humoral immune response against viral variants induced by vaccines over time is crucial for improving immunization protocols. We carried out a 6-month longitudinal prospective study in which 60 individuals between 21 and 71 years of age who have received the complete scheme of the BNT162b2 vaccine were followed to determine titers of serum neutralizing activity. The neutralizing capacity was measured at one, three, and six-months post-vaccination by plaque reduction neutralization assay using SARS-CoV-2 B.1 (D614G) and the Gamma, Alpha, Delta, and Mu variants. Data were analyzed using GraphPad 5.0. Neutralizing activity against five different SARS-CoV-2 variants was detected in the serum samples of all vaccinated participants to a different extent after one month, with a progressive decrease according to age and gender. Overall, after one month of vaccination, the neutralizing titer was lower for all evaluated variants when compared to B.1, most remarkable against Delta and Mu, with a reduction of 83.1% and 92.3%, respectively. In addition, the Titer at 3- or 6-months follow-up decreased dramatically for all variants. Our results support the decaying of serum neutralizing activity, both over time and across SARS-CoV-2 variants, being more significant in older men. Since Delta and Mu appear to evade the neutralizing activity, these and further new variants of immune escape mutations should be considered for novel vaccine formulations.
    MeSH term(s) Aged ; Antibodies, Neutralizing ; Antibodies, Viral ; BNT162 Vaccine ; COVID-19/prevention & control ; COVID-19 Vaccines ; Humans ; Male ; Prospective Studies ; SARS-CoV-2
    Chemical Substances Antibodies, Neutralizing ; Antibodies, Viral ; COVID-19 Vaccines ; BNT162 Vaccine (N38TVC63NU)
    Language English
    Publishing date 2022-05-02
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2022.879036
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: In vitro and in silico evaluation of antiretrovirals against SARS-CoV-2: A drug repurposing approach.

    Zapata-Cardona, Maria I / Florez-Alvarez, Lizdany / Guerra-Sandoval, Ariadna L / Chvatal-Medina, Mateo / Guerra-Almonacid, Carlos M / Hincapie-Garcia, Jaime / Hernandez, Juan C / Rugeles, Maria T / Zapata-Builes, Wildeman

    AIMS microbiology

    2023  Volume 9, Issue 1, Page(s) 20–40

    Abstract: Background: Drug repurposing is a valuable strategy for rapidly developing drugs for treating COVID-19. This study aimed to evaluate the antiviral effect of six antiretrovirals against SARS-CoV-2 in vitro and in silico.: Methods: The cytotoxicity of ... ...

    Abstract Background: Drug repurposing is a valuable strategy for rapidly developing drugs for treating COVID-19. This study aimed to evaluate the antiviral effect of six antiretrovirals against SARS-CoV-2 in vitro and in silico.
    Methods: The cytotoxicity of lamivudine, emtricitabine, tenofovir, abacavir, efavirenz and raltegravir on Vero E6 was evaluated by MTT assay. The antiviral activity of each of these compounds was evaluated via a pre-post treatment strategy. The reduction in the viral titer was assessed by plaque assay. In addition, the affinities of the antiretroviral interaction with viral targets RdRp (RNA-dependent RNA polymerase), ExoN-NSP10 (exoribonuclease and its cofactor, the non-structural protein 10) complex and 3CLpro (3-chymotrypsin-like cysteine protease) were evaluated by molecular docking.
    Results: Lamivudine exhibited antiviral activity against SARS-CoV-2 at 200 µM (58.3%) and 100 µM (66.7%), while emtricitabine showed anti-SARS-CoV-2 activity at 100 µM (59.6%), 50 µM (43.4%) and 25 µM (33.3%). Raltegravir inhibited SARS-CoV-2 at 25, 12.5 and 6.3 µM (43.3%, 39.9% and 38.2%, respectively). The interaction between the antiretrovirals and SARS-CoV-2 RdRp, ExoN-NSP10 and 3CLpro yielded favorable binding energies (from -4.9 kcal/mol to -7.7 kcal/mol) using bioinformatics methods.
    Conclusion: Lamivudine, emtricitabine and raltegravir showed in vitro antiviral effects against the D614G strain of SARS-CoV-2. Raltegravir was the compound with the greatest in vitro antiviral potential at low concentrations, and it showed the highest binding affinities with crucial SARS-CoV-2 proteins during the viral replication cycle. However, further studies on the therapeutic utility of raltegravir in patients with COVID-19 are required.
    Language English
    Publishing date 2023-01-16
    Publishing country United States
    Document type Journal Article
    ISSN 2471-1888
    ISSN (online) 2471-1888
    DOI 10.3934/microbiol.2023002
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Dynamics of humoral immune response in SARS-CoV-2 infected individuals with different clinical stages.

    Mendez-Cortina, Yorjagis / Rodriguez-Perea, Ana Lucía / Chvatal-Medina, Mateo / Lopera, Tulio Jose / Alvarez-Mesa, Natalia / Rodas-Marín, Jan Karlo / Moncada, Diana Carolina / Rugeles, Maria Teresa / Velilla, Paula Andrea

    Frontiers in immunology

    2022  Volume 13, Page(s) 1007068

    Abstract: Background: The COVID-19 pandemic remains a global health problem. As in other viral infections, the humoral immune response against SARS-CoV-2 is thought to be crucial for controlling the infection. However, the dynamic of B cells in the clinical ... ...

    Abstract Background: The COVID-19 pandemic remains a global health problem. As in other viral infections, the humoral immune response against SARS-CoV-2 is thought to be crucial for controlling the infection. However, the dynamic of B cells in the clinical spectrum of this disease is still controversial. This study aimed to characterize B cell subsets and neutralizing responses in COVID-19 patients according to disease severity through a one-month follow-up.
    Methods: A cohort of 71 individuals with SARS-CoV-2 infection confirmed by RT-PCR were recruited and classified into four groups: i) asymptomatic; ii) symptomatic outpatients; iii) hospitalized in ward, and iv) intensive care unit patients (ICU). Samples were taken at days 0 (inclusion to the study), 7 and 30. B cell subsets and neutralizing antibodies were assessed using multiparametric flow cytometry and plaque reduction neutralization, respectively.
    Results: Older age, male gender and body mass index over 25 were common factors among hospitalized and ICU patients, compared to those with milder clinical presentations. In addition, those requiring hospitalization had more comorbidities. A significant increase in the frequencies of CD19
    Conclusion: The humoral immune response is variable among SARS-CoV-2 infected people depending on the severity and time of clinical evolution. In severe COVID-19 patients, a higher plasmablast frequency and neutralizing antibody response were observed, suggesting that, despite having a robust humoral immunity, this response could be late, having a low impact on disease outcome.
    MeSH term(s) Humans ; Male ; SARS-CoV-2 ; Immunity, Humoral ; COVID-19 ; Pandemics ; Antibodies, Neutralizing
    Chemical Substances Antibodies, Neutralizing
    Language English
    Publishing date 2022-11-14
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2022.1007068
    Database MEDical Literature Analysis and Retrieval System OnLINE

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