Electrostatics Plays a Crucial Role in HIV-1 Protease Substrate Binding, Drugs Fail to Take Advantage

Biochemistry ◽  
2020 ◽  
Vol 59 (36) ◽  
pp. 3316-3331
Author(s):  
Mohd Ahsan ◽  
Chinmai Pindi ◽  
Sanjib Senapati
Keyword(s):  
Crucial Role ◽  
Substrate Binding ◽  
Protease Substrate ◽  
Hiv 1

scholarly journals HIV-1 Protease Substrate Binding and Product Release Pathways Explored with Coarse-Grained Molecular Dynamics

2007 ◽  
Vol 92 (12) ◽  
pp. 4179-4187 ◽  
Author(s):  
Joanna Trylska ◽  
Valentina Tozzini ◽  
Chia-en A. Chang ◽  
J. Andrew McCammon
Keyword(s):  
Molecular Dynamics ◽  
Substrate Binding ◽  
Coarse Grained ◽  
Product Release ◽  
Protease Substrate ◽  
Hiv 1 ◽  
Coarse Grained Molecular Dynamics

scholarly journals NUCKS1, a novel Tat coactivator, plays a crucial role in HIV-1 replication by increasing Tat-mediated viral transcription on the HIV-1 LTR promoter

Retrovirology ◽  
2014 ◽  
Vol 11 (1) ◽  
Author(s):  
Hye-Young Kim ◽  
Byeong-Sun Choi ◽  
Sung Soon Kim ◽  
Tae-Young Roh ◽  
Jihwan Park ◽  
...  
Keyword(s):  
Crucial Role ◽  
Viral Transcription ◽  
Ltr Promoter ◽  
Hiv 1

scholarly journals HIV-1 Tropism Testing and Clinical Management of CCR5 Antagonists: Quebec Review and Recommendations

2013 ◽  
Vol 24 (4) ◽  
pp. 202-208 ◽  
Author(s):  
Cécile Tremblay ◽  
Isabelle Hardy ◽  
Richard Lalonde ◽  
Benoit Trottier ◽  
Irina Tsarevsky ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Clinical Management ◽  
Crucial Role ◽  
Alternative Strategies ◽  
Limited Access ◽  
Ccr5 Receptor ◽  
Treatment Naïve ◽  
Ccr5 Antagonists ◽  
Phenotypic Tests ◽  
Hiv 1

HIV-1 tropism assays play a crucial role in determining the response to CCR5 receptor antagonists. Initially, phenotypic tests were used, but limited access to these tests prompted the development of alternative strategies. Recently, genotyping tropism has been validated using a Canadian technology in clinical trials investigating the use of maraviroc in both experienced and treatment-naive patients. The present guidelines review the evidence supporting the use of genotypic assays and provide recommendations regarding tropism testing in daily clinical management.

scholarly journals Host cell factors stimulate HIV-1 transcription by antagonizing substrate-binding function of Siah1 ubiquitin ligase to stabilize transcription elongation factor ELL2

2020 ◽  
Author(s):  
Jun Wu ◽  
Yuhua Xue ◽  
Xiang Gao ◽  
Qiang Zhou
Keyword(s):  
Host Cell ◽  
Stress Responses ◽  
Substrate Binding ◽  
Elongation Factor ◽  
Transcriptional Elongation ◽  
Elongation Complex ◽  
Binding Function ◽  
Cellular Stress Responses ◽  
Host Cell Factors ◽  
Hiv 1

Abstract The Siah1 and Siah2 ubiquitin ligases are implicated in diverse biological processes ranging from cellular stress responses, signaling to transcriptional regulation. A key substrate of Siah1 is ELL2, which undergoes proteolysis upon polyubiquitination. ELL2 stimulates transcriptional elongation and is a subunit of the Super Elongation Complex (SEC) essential for HIV-1 transactivation. Previously, multiple transcriptional and post-translational mechanisms are reported to control Siah's expression and activity. Here we show that the activity of Siah1/2 can also be suppressed by host cell factor 1 (HCF1), and the hitherto poorly characterized HCF2, which themselves are not degraded but can bind and block the substrate-binding domain (SBD) of Siah1/2 to prevent their autoubiquitination and trans-ubiquitination of downstream targets including ELL2. This effect stabilizes ELL2 and enhances the ELL2-SEC formation for robust HIV-1 transactivation. Thus, our study not only identifies HCF1/2 as novel activators of HIV-1 transcription through inhibiting Siah1 to stabilize ELL2, but also reveals the SBD of Siah1/2 as a previously unrecognized new target for HCF1/2 to exert this inhibition.

Where All the Roads Meet? A Cross Over Perspective on Host Factors Regulating SARS-CoV-2 Replication

2021 ◽  
Author(s):  
Sneh Lata ◽  
Ritu Mishra ◽  
Ravi Arya ◽  
Pooja Arora ◽  
Anismrita Lahon ◽  
...  
Keyword(s):  
Comparative Analysis ◽  
Crucial Role ◽  
Host Factors ◽  
Recent Issue ◽  
Genome Wide ◽  
Hiv 1

In the recent issue of Cell, four studies utilized genome wide CRISPR/Cas screens to identify host factors critical for the SARS-CoV-2 replication. We performed a comparative analysis of significant host factors (p<0.05) that were identified in these studies and found that fifteen candidates were common in at least three studies. Apart from ACE2 other common host factors included COG3, COG8, GDI2, ARPP19, SLC35B2, LIMA1, TLR9, VPS26A, CSNK2B, LRRN2, DDX51, ALG6, C1QTNF7 and BCOR. Interestingly, some of these host factors have been shown to be critical for other viruses including HIV-1, Dengue, Influenza, Zika etc., suggesting their crucial role in viral biology. Additionally, viral interactome of these host factors revealed that they were associated with several SARS-CoV-2 proteins as well. Hence, we present here, a comparative analysis of four genome wide screens against SARS-CoV-2, revealing common host factors that could be modulated to regulate SARS-CoV-2 and other viruses as well.

scholarly journals HIV-1 Protease-Substrate Coevolution in Nelfinavir Resistance

2014 ◽  
Vol 88 (13) ◽  
pp. 7145-7154 ◽  
Author(s):  
M. Kolli ◽  
A. Ozen ◽  
N. Kurt-Yilmaz ◽  
C. A. Schiffer
Keyword(s):  
Protease Substrate ◽  
Hiv 1
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