scholarly journals Active Components from Cassia abbreviata Prevent HIV-1 Entry by Distinct Mechanisms of Action

2021 ◽  
Vol 22 (9) ◽  
pp. 5052
Author(s):  
Yue Zheng ◽  
Xian-Wen Yang ◽  
Dominique Schols ◽  
Mattia Mori ◽  
Bruno Botta ◽  
...  
Keyword(s):  
Crude Extract ◽  
Female Genital Tract ◽  
Binding Activity ◽  
Sub Saharan Africa ◽  
Active Components ◽  
Chemical Structures ◽  
3D Space ◽  
In Silico Study ◽  
Sub Saharan ◽  
Hiv 1

Cassia abbreviata is widely used in Sub-Saharan Africa for treating many diseases, including HIV-1 infection. We have recently described the chemical structures of 28 compounds isolated from an alcoholic crude extract of barks and roots ofC. abbreviata, and showed that six bioactive compounds inhibit HIV-1 infection. In the present study, we demonstrate that the six compounds block HIV-1 entry into cells: oleanolic acid, palmitic acid, taxifolin, piceatannol, guibourtinidol-(4α®8)-epiafzelechin, and a novel compound named as cassiabrevone. We report, for the first time, that guibourtinidol-(4α®8)-epiafzelechin and cassiabrevone inhibit HIV-1 entry (IC50 of 42.47 µM and 30.96 µM, respectively), as well as that piceatannol interacts with cellular membranes. Piceatannol inhibits HIV-1 infection in a dual-chamber assay mimicking the female genital tract, as well as HSV infection, emphasizing its potential as a microbicide. Structure-activity relationships (SAR) showed that pharmacophoric groups of piceatannol are strictly required to inhibit HIV-1 entry. By a ligand-based in silico study, we speculated that piceatannol and norartocarpetin may have a very similar mechanism of action and efficacy because of the highly comparable pharmacophoric and 3D space, while guibourtinidol-(4α®8)-epiafzelechin and cassiabrevone may display a different mechanism. We finally show that cassiabrevone plays a major role of the crude extract of CA by blocking the binding activity of HIV-1 gp120 and CD4.

scholarly journals Evidence for both Intermittent and Persistent Compartmentalization of HIV-1 in the Female Genital Tract

2019 ◽  
Vol 93 (10) ◽  
Author(s):  
Batsirai M. Mabvakure ◽  
Bronwen E. Lambson ◽  
Kavisha Ramdayal ◽  
Lindi Masson ◽  
Dale Kitchin ◽  
...  
Keyword(s):  
Genital Tract ◽  
Statistical Tests ◽  
Female Genital Tract ◽  
Sub Saharan Africa ◽  
Subtype C ◽  
Genetic Features ◽  
Sieve Effect ◽  
Sub Saharan ◽  
Hiv 1 ◽  
Female Genital

ABSTRACTHIV-1 has been shown to evolve independently in different anatomical compartments, but studies in the female genital tract have been inconclusive. Here, we examined evidence of compartmentalization using HIV-1 subtype C envelope (Env) glycoprotein genes (gp160) obtained from matched cervicovaginal lavage (CVL) and plasma samples over 2 to 3 years of infection. HIV-1 gp160 amplification from CVL was achieved for only 4 of 18 acutely infected women, and this was associated with the presence of proinflammatory cytokines and/or measurable viremia in the CVL. Maximum likelihood trees and divergence analyses showed that all four individuals had monophyletic compartment-specific clusters of CVL- and/or plasma-derived gp160 sequences at all or some time points. However, two participants (CAP177 and CAP217) had CVL gp160 diversity patterns that differed from those in plasma and showed restricted viral flow from the CVL. Statistical tests of compartmentalization revealed evidence of persistent compartment-specific gp160 evolution in CAP177, while in CAP217 this was intermittent. Lastly, we identified several Env sites that distinguished viruses in these two compartments; for CAP177, amino acid differences arose largely through positive selection, while insertions/deletions were more common in CAP217. In both cases these differences contributed to substantial charge changes spread across the Env. Our data indicate that, in some women, HIV-1 populations within the genital tract can have Env genetic features that differ from those of viruses in plasma, which could impact the sensitivity of viruses in the genital tract to vaginal microbicides and vaccine-elicited antibodies.IMPORTANCEMost HIV-1 infections in sub-Saharan Africa are acquired heterosexually through the genital mucosa. Understanding the properties of viruses replicating in the female genital tract, and whether these properties differ from those of more commonly studied viruses replicating in the blood, is therefore important. Using longitudinal CVL and plasma-derived sequences from four HIV-1 subtype C-infected women, we found fewer viral migrations from the genital tract to plasma than in the opposite direction, suggesting a mucosal sieve effect from the genital tract to the blood compartment. Evidence for both persistent and intermittent compartmentalization between the genital tract and plasma viruses during chronic infection was detected in two of four individuals, perhaps explaining previously conflicting findings. In cases where compartmentalization occurred, comparison of CVL- and plasma-derived HIV sequences indicated that distinct features of viral populations in the CVL may affect the efficacy of microbicides and vaccines designed to provide mucosal immunity.

scholarly journals A Randomized Switch From Nevirapine-Based Antiretroviral Therapy to Single Tablet Rilpivirine/Emtricitabine/Tenofovir Disoproxil Fumarate in Virologically Suppressed Human Immunodeficiency Virus-1-Infected Rwandans

2016 ◽  
Vol 3 (3) ◽  
Author(s):  
Sean E. Collins ◽  
Philip M. Grant ◽  
Francois Uwinkindi ◽  
Annie Talbot ◽  
Eric Seruyange ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Antiretroviral Therapy ◽  
Tenofovir Disoproxil Fumarate ◽  
Sub Saharan Africa ◽  
Current Therapy ◽  
Virologic Suppression ◽  
Open Label ◽  
Immunodeficiency Virus ◽  
Sub Saharan ◽  
Hiv 1

Abstract Background.  Many human immunodeficiency virus (HIV)-infected patients remain on nevirapine-based antiretroviral therapy (ART) despite safety and efficacy concerns. Switching to a rilpivirine-based regimen is an alternative, but there is little experience with rilpivirine in sub-Saharan Africa where induction of rilpivirine metabolism by nevirapine, HIV subtype, and dietary differences could potentially impact efficacy. Methods.  We conducted an open-label noninferiority study of virologically suppressed (HIV-1 ribonucleic acid [RNA] < 50 copies/mL) HIV-1-infected Rwandan adults taking nevirapine plus 2 nucleos(t)ide reverse-transcriptase inhibitors. One hundred fifty participants were randomized 2:1 to switch to coformulated rilpivirine-emtricitabine-tenofovir disoproxil fumarate (referenced as the Switch Arm) or continue current therapy. The primary efficacy endpoint was HIV-1 RNA < 200 copies/mL at week 24 assessed by the US Food and Drug Administration Snapshot algorithm with a noninferiority margin of 12%. Results.  Between April and September 2014, 184 patients were screened, and 150 patients were enrolled; 99 patients switched to rilpivirine-emtricitabine-tenofovir, and 51 patients continued their nevirapine-based ART. The mean age was 42 years and 43% of participants were women. At week 24, virologic suppression (HIV-1 RNA level <200 copies/mL) was maintained in 93% and 92% in the Switch Arm versus the continuation arm, respectively. The Switch Arm was noninferior to continued nevirapine-based ART (efficacy difference 0.8%; 95% confidence interval, −7.5% to +12.0%). Both regimens were generally safe and well tolerated, although 2 deaths, neither attributed to study medications, occurred in participants in the Switch Arm. Conclusions.  A switch from nevirapine-based ART to rilpivirine-emtricitabine-tenofovir disoproxil fumarate had similar virologic efficacy to continued nevirapine-based ART after 24 weeks with few adverse events.

scholarly journals HIV-1 Full-Genome Phylogenetics of Generalized Epidemics in Sub-Saharan Africa: Impact of Missing Nucleotide Characters in Next-Generation Sequences

2017 ◽  
Vol 33 (11) ◽  
pp. 1083-1098 ◽  
Author(s):  
Oliver Ratmann ◽  
Chris Wymant ◽  
Caroline Colijn ◽  
Siva Danaviah ◽  
Max Essex ◽  
...  
Keyword(s):  
Sub Saharan Africa ◽  
Full Genome ◽  
Next Generation ◽  
Sub Saharan ◽  
Hiv 1

scholarly journals Prediction of extended high viremia among newly HIV-1-infected persons in sub-Saharan Africa

PLoS ONE ◽  
2018 ◽  
Vol 13 (4) ◽  
pp. e0192785 ◽  
Author(s):  
Kimberly A. Powers ◽  
Matthew A. Price ◽  
Etienne Karita ◽  
Anatoli Kamali ◽  
William Kilembe ◽  
...  
Keyword(s):  
Sub Saharan Africa ◽  
Sub Saharan ◽  
Hiv 1

scholarly journals New Subtype B Containing HIV-1 Circulating Recombinant of sub-Saharan Africa Origin in Nigerian Men Who Have Sex With Men

2019 ◽  
Vol 81 (5) ◽  
pp. 578-584 ◽  
Author(s):  
Erik Billings ◽  
Gustavo H. Kijak ◽  
Eric Sanders-Buell ◽  
Nicaise Ndembi ◽  
Anne Marie OʼSullivan ◽  
...  
Keyword(s):  
Sub Saharan Africa ◽  
Subtype B ◽  
Nigerian Men ◽  
Sub Saharan ◽  
Sex With Men ◽  
Hiv 1

Prognostic Value of Virological and Immunological Responses After 6 Months of Antiretroviral Treatment in Adults With HIV-1 Infection in Sub-Saharan Africa

2012 ◽  
Vol 59 (3) ◽  
pp. 236-244 ◽  
Author(s):  
Andrea De Luca ◽  
Maria Cristina Marazzi ◽  
Sandro Mancinelli ◽  
Susanna Ceffa ◽  
Anna Maria Doro Altan ◽  
...  
Keyword(s):  
Prognostic Value ◽  
Antiretroviral Treatment ◽  
Sub Saharan Africa ◽  
Immunological Responses ◽  
Sub Saharan ◽  
Hiv 1

Study of bias in antenatal clinic HIV-1 surveillance data in a high contraceptive prevalence population in sub-Saharan Africa

AIDS ◽  
2002 ◽  
Vol 16 (4) ◽  
pp. 643-652 ◽  
Author(s):  
Simon Gregson ◽  
Nicola Terceira ◽  
Memory Kakowa ◽  
Peter R. Mason ◽  
Roy M. Anderson ◽  
...  
Keyword(s):  
Antenatal Clinic ◽  
Surveillance Data ◽  
Sub Saharan Africa ◽  
Contraceptive Prevalence ◽  
Sub Saharan ◽  
Hiv 1

Transmission of HIV-1 infection in sub-Saharan Africa and effect of elimination of unsafe injections

The Lancet ◽  
2004 ◽  
Vol 363 (9407) ◽  
pp. 482-488 ◽  
Author(s):  
George P Schmid ◽  
Anne Buvé ◽  
Peter Mugyenyi ◽  
Geoff P Garnett ◽  
Richard J Hayes ◽  
...  
Keyword(s):  
Sub Saharan Africa ◽  
Sub Saharan ◽  
Unsafe Injections ◽  
Hiv 1
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