Inhibitors of HIV-1 Proteinase Containing 2-Heterosubstituted 4-Amino-3-hydroxy-5-phenylpentanoic Acid: Synthesis, Enzyme Inhibition, and Antiviral Activity

1994 ◽  
Vol 37 (19) ◽  
pp. 3079-3089 ◽  
Author(s):  
Dieter Scholz ◽  
Andreas Billich ◽  
Brigitte Charpiot ◽  
Peter Ettmayer ◽  
Philipp Lehr ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Enzyme Inhibition ◽  
Acid Synthesis ◽  
Hiv 1

A series of potent HIV-1 protease inhibitors containing a hydroxyethyl secondary amine transition state isostere: synthesis, enzyme inhibition, and antiviral activity

1992 ◽  
Vol 35 (14) ◽  
pp. 2525-2533 ◽  
Author(s):  
Thomas J. Tucker ◽  
William C. Lumma ◽  
Linda S. Payne ◽  
Jenny M. Wai ◽  
S. Jane De Solms ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Transition State ◽  
Protease Inhibitors ◽  
Enzyme Inhibition ◽  
Secondary Amine ◽  
Hiv 1

scholarly journals Potent HIV‐1 Protease Inhibitors Containing Carboxylic and Boronic Acids: Effect on Enzyme Inhibition and Antiviral Activity and Protein‐Ligand X‐ray Structural Studies

ChemMedChem ◽  
2019 ◽  
Vol 14 (21) ◽  
pp. 1863-1872 ◽  
Author(s):  
Arun K. Ghosh ◽  
Zilei Xia ◽  
Satish Kovela ◽  
William L. Robinson ◽  
Megan E. Johnson ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Protease Inhibitors ◽  
Enzyme Inhibition ◽  
Boronic Acids ◽  
Structural Studies ◽  
X Ray ◽  
Hiv 1

scholarly journals SUMOylation of SAMHD1 at Lysine 595 is required for HIV-1 restriction in non-cycling cells

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Charlotte Martinat ◽  
Arthur Cormier ◽  
Joëlle Tobaly-Tapiero ◽  
Noé Palmic ◽  
Nicoletta Casartelli ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Reverse Transcription ◽  
Immune Cells ◽  
Viral Restriction ◽  
Antiviral Function ◽  
Hiv 1 ◽  
Constitutively Active

AbstractSAMHD1 is a cellular triphosphohydrolase (dNTPase) proposed to inhibit HIV-1 reverse transcription in non-cycling immune cells by limiting the supply of the dNTP substrates. Yet, phosphorylation of T592 downregulates SAMHD1 antiviral activity, but not its dNTPase function, implying that additional mechanisms contribute to viral restriction. Here, we show that SAMHD1 is SUMOylated on residue K595, a modification that relies on the presence of a proximal SUMO-interacting motif (SIM). Loss of K595 SUMOylation suppresses the restriction activity of SAMHD1, even in the context of the constitutively active phospho-ablative T592A mutant but has no impact on dNTP depletion. Conversely, the artificial fusion of SUMO2 to a non-SUMOylatable inactive SAMHD1 variant restores its antiviral function, a phenotype that is reversed by the phosphomimetic T592E mutation. Collectively, our observations clearly establish that lack of T592 phosphorylation cannot fully account for the restriction activity of SAMHD1. We find that SUMOylation of K595 is required to stimulate a dNTPase-independent antiviral activity in non-cycling immune cells, an effect that is antagonized by cyclin/CDK-dependent phosphorylation of T592 in cycling cells.

scholarly journals Design, Synthesis, and antiviral activity of a series of CD4-mimetic small-molecule HIV-1 entry inhibitors

2021 ◽  
pp. 116000
Author(s):  
Francesca Curreli ◽  
Shahad Ahmed ◽  
Sofia M. Benedict Victor ◽  
Ildar R. Iusupov ◽  
Evgeny A. Spiridonov ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Small Molecule ◽  
Design Synthesis ◽  
Entry Inhibitors ◽  
Hiv 1

scholarly journals Flavonol 7-O-Glucoside Herbacitrin Inhibits HIV-1 Replication through Simultaneous Integrase and Reverse Transcriptase Inhibition

2019 ◽  
Vol 2019 ◽  
pp. 1-6 ◽  
Author(s):  
Éva Áy ◽  
Attila Hunyadi ◽  
Mária Mezei ◽  
János Minárovits ◽  
Judit Hohmann
Keyword(s):  
Antiviral Activity ◽  
Reverse Transcriptase ◽  
Cell Cultures ◽  
Core Protein ◽  
Integrase Inhibitor ◽  
Host Cells ◽  
Cytotoxic Activities ◽  
Protein Levels ◽  
Hiv 1 ◽  
Antiretroviral Activity

Here we report the evaluation of the antiretroviral effect of two flavonoid 7-O-glucosides, herbacitrin (1) and gossypitrin (2), together with quercetin (3), a well-studied flavonol. Antiviral activity of the flavonoids was assessed by analyzing HIV-1 p24 core protein levels in the supernatants of HIV-1 infected MT-4 and MT-2 cell cultures. The compounds showed mild to weak cytotoxic activities on the host cells; herbacitrin was the strongest in this regard (CC50=27.8 and 63.64 μM on MT-4 and MT-2 cells, respectively). In nontoxic concentrations, herbacitrin and quercetin reduced HIV-1 replication, whereas gossypitrin was ineffective. Herbacitrin was found to inhibit reverse transcriptase at 21.5 μM, while it was a more potent integrase inhibitor already active at 2.15 μM. Therefore, our observations suggest that herbacitrin exerts antiretroviral activity through simultaneously acting on these two targets of HIV-1 and that integrase inhibition might play a major role in this activity.

scholarly journals Antiviral activity of derivatized dextrans on HIV-1 infection of primary macrophages and blood lymphocytes

1997 ◽  
Vol 1362 (1) ◽  
pp. 47-55 ◽  
Author(s):  
Nabila Seddiki ◽  
Elisabeth Mbemba ◽  
Didier Letourneur ◽  
Loyda Ylisastigui ◽  
Abdelaziz Benjouad ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Blood Lymphocytes ◽  
Hiv 1

scholarly journals Towards Inhibition of Vif-APOBEC3G Interaction: Which Protein to Target?

2010 ◽  
Vol 2010 ◽  
pp. 1-10 ◽  
Author(s):  
Iris Cadima-Couto ◽  
Joao Goncalves
Keyword(s):  
Antiviral Activity ◽  
Protein Binding ◽  
Mechanism Of Action ◽  
Cellular Immunity ◽  
Viral Infectivity ◽  
Binding Partners ◽  
Viral Infectivity Factor ◽  
Vif Protein ◽  
Hiv 1 ◽  
Antiretroviral Activity

APOBEC proteins appeared in the cellular battle against HIV-1 as part of intrinsic cellular immunity. The antiretroviral activity of some of these proteins is overtaken by the action of HIV-1 Viral Infectivity Factor (Vif) protein. Since the discovery of APOBEC3G (A3G) as an antiviral factor, many advances have been made to understand its mechanism of action in the cell and how Vif acts in order to counteract its activity. The mainstream concept is that Vif overcomes the innate antiviral activity of A3G by direct protein binding and promoting its degradation via the cellular ubiquitin/proteasomal pathway. Vif may also inhibit A3G through mechanisms independent of proteasomal degradation. Binding of Vif to A3G is essential for its degradation since disruption of this interaction is predicted to stimulate intracellular antiviral immunity. In this paper we will discuss the different binding partners between both proteins as one of the major challenges for the development of new antiviral drugs.

scholarly journals In Vitro Antiviral Activity and Cross-Resistance Profile of PL-100, a Novel Protease Inhibitor of Human Immunodeficiency Virus Type 1

2007 ◽  
Vol 51 (11) ◽  
pp. 4036-4043 ◽  
Author(s):  
Serge Dandache ◽  
Guy Sévigny ◽  
Jocelyn Yelle ◽  
Brent R. Stranix ◽  
Neil Parkin ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Antiviral Activity ◽  
Highly Active Antiretroviral Therapy ◽  
Cross Resistance ◽  
Drug Resistant ◽  
Resistance Profile ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT Despite the success of highly active antiretroviral therapy, the current emergence and spread of drug-resistant variants of human immunodeficiency virus (HIV) stress the need for new inhibitors with distinct properties. We designed, produced, and screened a library of compounds based on an original l-lysine scaffold for their potentials as HIV type 1 (HIV-1) protease inhibitors (PI). One candidate compound, PL-100, emerged as a specific and noncytotoxic PI that exhibited potent inhibition of HIV-1 protease and viral replication in vitro (Ki , ∼36 pM, and 50% effective concentration [EC50], ∼16 nM, respectively). To confirm that PL-100 possessed a favorable resistance profile, we performed a cross-resistance study using a panel of 63 viral strains from PI-experienced patients selected for the presence of primary PI mutations known to confer resistance to multiple PIs now in clinical use. The results showed that PL-100 retained excellent antiviral activity against almost all of these PI-resistant viruses and that its performance in this regard was superior to those of atazanavir, amprenavir, indinavir, lopinavir, nelfinavir, and saquinavir. In almost every case, the increase in the EC50 for PL-100 observed with viruses containing multiple mutations in protease was far less than that obtained with the other drugs tested. These data underscore the potential for PL-100 to be used in the treatment of drug-resistant HIV disease and argue for its further development.

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