First large scale chemical synthesis of the 72 amino acid HIV-1 nucleocapsid protein NCp7 in an active form

1991 ◽  
Vol 180 (2) ◽  
pp. 1010-1018 ◽  
Author(s):  
H. de Rocquigny ◽  
D. Ficheux ◽  
C. Gabus ◽  
M.-C. Fournié-Zaluski ◽  
J.-L. Darlix ◽  
...  
Biochemistry ◽  
2004 ◽  
Vol 43 (14) ◽  
pp. 4304-4312 ◽  
Author(s):  
József Tözsér ◽  
Sergey Shulenin ◽  
John M. Louis ◽  
Terry D. Copeland ◽  
Stephen Oroszlan

2017 ◽  
Author(s):  
C. K. Sruthi ◽  
Meher K. Prakash

ABSTRACTViruses are simultaneously simple and complex. Simple because they have barely around ten types of proteins compared to tens of thousands of proteins in bacteria. Complex because amino acid mutation rates are very high, challenging host immune system and drugs. In this work we use the co-evolution of amino acids and the network characteristics that arise out of it to describe the complexity hidden in the multitude of variations in a viral genome. Using large-scale genomic data, the complexity in several viruses was compared. Interestingly, the co-evolutionary relations were primarily intra-protein in avian influenza and inter-protein in HIV-1. The network degree distributions showed two universality classes: a power-law with exponent −1 in HIV-1 and avian-influenza, random co-evolutionary behavior in human flu and dengue, suggesting the co-evolution as one way to statistically classify the complexity in viruses. The observed correlation between the network densities and the strengths on virus Richter scale raises interesting questions on whether it is possible to define the complexity of viruses using their evolutionary networks.


1994 ◽  
Vol 242 (4) ◽  
pp. 422-429 ◽  
Author(s):  
Gerd Müller ◽  
Bettina Strack ◽  
Jens Dannull ◽  
Brian S. Sproat ◽  
Andrej Surovoy ◽  
...  

2020 ◽  
Vol 26 (8) ◽  
pp. 802-814 ◽  
Author(s):  
Nemanja Turkovic ◽  
Branka Ivkovic ◽  
Jelena Kotur-Stevuljevic ◽  
Milica Tasic ◽  
Bojan Marković ◽  
...  

Background: Since the beginning of the HIV/AIDS epidemic, 75 million people have been infected with the HIV and about 32 million people have died of AIDS. Investigation of the molecular mechanisms critical to the HIV replication cycle led to the identification of potential drug targets for AIDS therapy. One of the most important discoveries is HIV-1 protease, an enzyme that plays an essential role in the replication cycle of HIV. Objective: The aim of the present study is to synthesize and investigate anti-HIV-1 protease activity of some chalcone derivatives with the hope of discovering new lead structure devoid drug resistance. Methods: 20 structurally similar chalcone derivatives were synthesized and their physico-chemical characterization was performed. Binding of chalcones to HIV-1 protease was investigated by fluorimetric assay. Molecular docking studies were conducted to understand the interactions. Results: The obtained results revealed that all compounds showed anti-HIV-1 protease activity. Compound C1 showed the highest inhibitory activity with an IC50 value of 0.001 μM, which is comparable with commercial product Darunavir. Conclusion: It is difficult to provide general principles of inhibitor design. Structural properties of the compounds are not the only consideration; ease of chemical synthesis, low molecular weight, bioavailability, and stability are also of crucial importance. Compared to commercial products the main advantage of compound C1 is the ease of chemical synthesis and low molecular weight. Furthermore, compound C1 has a structure that is different to peptidomimetics, which could contribute to its stability and bioavailability.


PLoS ONE ◽  
2010 ◽  
Vol 5 (9) ◽  
pp. e12463 ◽  
Author(s):  
Morgane Rolland ◽  
Jonathan M. Carlson ◽  
Siriphan Manocheewa ◽  
J. Victor Swain ◽  
Erinn Lanxon-Cookson ◽  
...  

Marine Drugs ◽  
2021 ◽  
Vol 19 (5) ◽  
pp. 241
Author(s):  
Shaden A. M. Khalifa ◽  
Eslam S. Shedid ◽  
Essa M. Saied ◽  
Amir Reza Jassbi ◽  
Fatemeh H. Jamebozorgi ◽  
...  

Cyanobacteria are photosynthetic prokaryotic organisms which represent a significant source of novel, bioactive, secondary metabolites, and they are also considered an abundant source of bioactive compounds/drugs, such as dolastatin, cryptophycin 1, curacin toyocamycin, phytoalexin, cyanovirin-N and phycocyanin. Some of these compounds have displayed promising results in successful Phase I, II, III and IV clinical trials. Additionally, the cyanobacterial compounds applied to medical research have demonstrated an exciting future with great potential to be developed into new medicines. Most of these compounds have exhibited strong pharmacological activities, including neurotoxicity, cytotoxicity and antiviral activity against HCMV, HSV-1, HHV-6 and HIV-1, so these metabolites could be promising candidates for COVID-19 treatment. Therefore, the effective large-scale production of natural marine products through synthesis is important for resolving the existing issues associated with chemical isolation, including small yields, and may be necessary to better investigate their biological activities. Herein, we highlight the total synthesized and stereochemical determinations of the cyanobacterial bioactive compounds. Furthermore, this review primarily focuses on the biotechnological applications of cyanobacteria, including applications as cosmetics, food supplements, and the nanobiotechnological applications of cyanobacterial bioactive compounds in potential medicinal applications for various human diseases are discussed.


Viruses ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1092
Author(s):  
János András Mótyán ◽  
Márió Miczi ◽  
Stephen Oroszlan ◽  
József Tőzsér

To explore the sequence context-dependent nature of the human immunodeficiency virus type 1 (HIV-1) protease’s specificity and to provide a rationale for viral mutagenesis to study the potential role of the nucleocapsid (NC) processing in HIV-1 replication, synthetic oligopeptide substrates representing the wild-type and modified versions of the proximal cleavage site of HIV-1 NC were assayed as substrates of the HIV-1 protease (PR). The S1′ substrate binding site of HIV-1 PR was studied by an in vitro assay using KIVKCF↓NCGK decapeptides having amino acid substitutions of N17 residue of the cleavage site of the first zinc-finger domain, and in silico calculations were also performed to investigate amino acid preferences of S1′ site. Second site substitutions have also been designed to produce “revertant” substrates and convert a non-hydrolysable sequence (having glycine in place of N17) to a substrate. The specificity constants obtained for peptides containing non-charged P1′ substitutions correlated well with the residue volume, while the correlation with the calculated interaction energies showed the importance of hydrophobicity: interaction energies with polar residues were related to substantially lower specificity constants. Cleavable “revertants” showed one residue shift of cleavage position due to an alternative productive binding mode, and surprisingly, a double cleavage of a substrate was also observed. The results revealed the importance of alternative binding possibilities of substrates into the HIV-1 PR. The introduction of the “revertant” mutations into infectious virus clones may provide further insights into the potential role of NC processing in the early phase of the viral life-cycle.


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