scholarly journals Design and Identification of Potential HIV-1 Entry Inhibitors Using In Silico Click Chemistry and Molecular Modeling Methods

Author(s):  
A.M. Andrianov ◽  
A.M. Yushkevich ◽  
I.P. Bosko ◽  
A.D. Karpenko ◽  
Yu.V. Kornoushenko ◽  
...  

An integrated approach including the click chemistry methodology, molecular docking, quantum mechanics, and molecular dynamics was used to computer-aided design of potential HIV-1 inhibitors able to block the membrane-proximal external region (MPER) of HIV-1 gp41, which plays an important role in the fusion of the viral and host cell membranes. Evaluation of the binding efficiency of the designed compounds to the HIV-1 MPER peptide was performed using the methods of molecular modeling, resulting in nine chemical compounds exhibiting high-affinity binding to this functionally important site of the trimeric “spike” of the viral envelope. The data obtained indicate that the identified compounds are promising for the development of novel antiviral drugs, HIV fusion inhibitors blocking the early stages of HIV infection.

Author(s):  
A. M. Andrianov ◽  
A. M. Yushkevich ◽  
I. P. Bosko ◽  
A. D. Karpenko ◽  
Yu. V. Kornoushenko ◽  
...  

An integrated approach including the click chemistry methodology, molecular docking, quantum mechanics, and molecular dynamics was used to perform the computer-aided design of potential HIV-1 inhibitors able to block the membrane- proximal external region (MPER) of HIV-1 gp41 that plays an important role in the fusion of the viral and host cell membranes. Evaluation of the binding efficiency of the designed compounds to the HIV-1 MPER peptide was performed using the methods of molecular modeling, resulting in nine chemical compounds that exhibit the high-affinity binding to this functionally important site of the trimeric “spike” of the viral envelope. The data obtained indicate that the identified compounds are promising for the development of novel antiviral drugs, HIV fusion inhibitors blocking the early stages of HIV infection.


2013 ◽  
Vol 31 (sup1) ◽  
pp. 126-126
Author(s):  
Alexander M. Andrianov ◽  
Yuri V. Kornoushenko ◽  
Ivan A. Kashyn ◽  
Alexander V. Tuzikov

2011 ◽  
Vol 7 (4) ◽  
pp. 309-316 ◽  
Author(s):  
Jian Jun Tan ◽  
Bin Zhang ◽  
Xiao Jing Cong ◽  
Lei Fu Yang ◽  
Bin Liu ◽  
...  

2012 ◽  
Vol 28 (6) ◽  
pp. 468-476 ◽  
Author(s):  
A. M. Andrianov ◽  
I. V. Anishchenko ◽  
M. A. Kisel ◽  
Yu. V. Kornoushenko ◽  
V. A. Nikolayevich ◽  
...  

Viruses ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 746 ◽  
Author(s):  
Alexander M. Andrianov ◽  
Grigory I. Nikolaev ◽  
Yuri V. Kornoushenko ◽  
Wei Xu ◽  
Shibo Jiang ◽  
...  

Despite recent progress in the development of novel potent HIV-1 entry/fusion inhibitors, there are currently no licensed antiviral drugs based on inhibiting the critical interactions of the HIV-1 envelope gp120 protein with cellular receptor CD4. In this connection, studies on the design of new small-molecule compounds able to block the gp120-CD4 binding are still of great value. In this work, in silico design of drug-like compounds containing the moieties that make the ligand active towards gp120 was performed within the concept of click chemistry. Complexes of the designed molecules bound to gp120 were then generated by molecular docking and optimized using semiempirical quantum chemical method PM7. Finally, the binding affinity analysis of these ligand/gp120 complexes was performed by molecular dynamic simulations and binding free energy calculations. As a result, five top-ranking compounds that mimic the key interactions of CD4 with gp120 and show the high binding affinity were identified as the most promising CD4-mimemic candidates. Taken together, the data obtained suggest that these compounds may serve as promising scaffolds for the development of novel, highly potent and broad anti-HIV-1 therapeutics.


Procedia CIRP ◽  
2016 ◽  
Vol 50 ◽  
pp. 305-310 ◽  
Author(s):  
Jean-Bernard Bluntzer ◽  
Egon Ostrosi ◽  
Jérémy Niez

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