Maraviroc, tenofovir disoproxil fumarate and dapivirine, activate progesterone receptor B in the absence progestogens.

Maraviroc, tenofovir disoproxil fumarate and dapivirine, activate progesterone receptor B in the absence progestogens. Biochem Biophys Res Commun. 2020 Oct 01;: Authors: Enfield K, Dlamini S, Avenant C, Kuipa M, Hapgood JP Abstract Antiretroviral therapy has slowed the HIV/AIDS pandemic and is currently being used as a prophylactic measure for individuals at high risk of infection. However, concerns over adverse effects of long-term use need to be explored. We hypothesize that this may occur, at least in part, through off-target effects via select steroid receptors (SRs) that broadly regulate multiple physiological processes. We investigated the effects of maraviroc (MVC), tenofovir disoproxil fumarate (TDF), and dapivirine (DPV) on progesterone receptor B (PR-B) transcriptional activity. We found that MVC and TDF activate PR-B transcription in the absence of progestogens on a PR-regulated promoter reporter construct and on endogenous PR-regulated genes. MVC and TDF exhibited no direct binding to PR-B; however, increased PR-B phosphorylation was detected with TDF but not MVC. DPV transactivated gilz and ptgs2 in the absence of progestogens and exhibited PR-B binding while showing no effects on phosphorylation, suggesting that it may activate PR-B through a direct mechanism. Our study shows that potential off-target immunomodulatory effects of MVC, TDF and DPV occur in vitro and these are most likely mediated by different mechanisms of PR-B activatio...
Source: Biochemical and Biophysical Research communications - Category: Biochemistry Authors: Tags: Biochem Biophys Res Commun Source Type: research

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Source: Current Opinion in HIV and AIDS - Category: Infectious Diseases Tags: COVID19: Edited by Zhiwei Chen and Linqui Zhang Source Type: research
Purpose of review Coronavirus disease 2019 (COVID-19) is a highly contagious and potentially lethal pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). No specific antiviral treatment is currently available. The purpose of this review is to highlight the main repurposed drug treatments with in-vitro or in-vivo efficacy against the SARS-CoV-2. Recent findings Recent clinical trials suggested remdesivir, IFN-β-1b and favipiravir have potential clinical and/or virological benefits on patients with COVID-19. Short course of stress dose of corticosteroids might be used as adjunctive tr...
Source: Current Opinion in HIV and AIDS - Category: Infectious Diseases Tags: COVID19: Edited by Zhiwei Chen and Linqui Zhang Source Type: research
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