In the absence of an effective vaccine against HIV-1 infection, anti-HIV-1 strategies play a major role in disease control. However, the rapid emergence of drug resistance against all currently used anti-HIV-1 molecules necessitates the development of new antiviral molecules and/or strategies against HIV-1 infection. In this study, we have identified a benzamide derivative named AH0109 that exhibits potent anti-HIV-1 activity at an 50% effective concentration of 0.7 μM in HIV-1-susceptible CD4(+) C8166 T cells. Mechanistic analysis revealed that AH0109 significantly inhibits both HIV-1 reverse transcription and viral cDNA nuclear import. Furthermore, our infection experiments indicated that AH0109 is capable of disrupting the replication of HIV-1 strains that are resistant to the routinely used anti-HIV-1 drugs zidovudine, lamivudine, nevirapine, and raltegravir. Together, these findings provide evidence for a newly identified antiviral molecule that can potentially be developed as an anti-HIV-1 agent.
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http://dx.doi.org/10.1128/AAC.00100-13 | DOI Listing |
mBio
January 2025
Department of Infectious Diseases and Immunology, Clinical Research Center, National Hospital Organization Nagoya Medical Center, Nagoya, Aichi, Japan.
The human cellular cytidine deaminases APOBEC3s (A3s) inhibit virion infectivity factor (Vif)-deficient HIV-1 replication. However, virus-encoded Vifs abolish this defense system by specifically recruiting A3s to an E3 ubiquitin ligase complex to induce their degradation. The highly conserved Vif PPLP motif is critical for the Vif-mediated antagonism of A3s and is believed to be important for Vif multimerization.
View Article and Find Full Text PDFFront Immunol
January 2025
Department I of Internal Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.
Antiretroviral therapy is the standard treatment for HIV, but it requires daily use and can cause side effects. Despite being available for decades, there are still 1.5 million new infections and 700,000 deaths each year, highlighting the need for better therapies.
View Article and Find Full Text PDFVirol J
January 2025
Laboratório de Desenvolvimento Tecnológico em Virologia, Instituto Oswaldo cruz, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brasil.
Background: Nonenveloped viruses, such as hepatitis A virus (HAV) and parvovirus B19 (B19V), are not inactivated by detergents and solvents commonly used to manufacture plasma derivatives. Cases of transfusion-transmitted HAV and B19V have already been described in several countries. This study aimed to determine the incidence of HAV and B19V asymptomatic infections in blood donors from Rio de Janeiro and evaluate the residual risk of transmission to blood derivative recipients.
View Article and Find Full Text PDFNat Med
January 2025
Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Long-term risks of gene therapy are not fully understood. In this study, we evaluated safety outcomes in 783 patients over more than 2,200 total patient-years of observation from 38 T cell therapy trials. The trials employed integrating gammaretroviral or lentiviral vectors to deliver engineered receptors to target HIV-1 infection or cancer.
View Article and Find Full Text PDFBackground: Recent declines in HIV incidence among adolescent girls and young women (AGYW) in Africa are often attributed to the expansion of biomedical interventions such as antiretroviral therapy and voluntary medical male circumcision. However, changes in sexual behaviour may also play a critical role. Understanding the relative contributions of these factors is essential for developing strategies to sustain and further reduce HIV transmission.
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