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Coevolution analysis of amino-acids reveals diversified drug-resistance solutions in viral sequences: a case study of hepatitis B virus

2020 Virus Evolution  
Primary and compensatory mutations have been associated with lamivudine resistance, whereas more complex mutational patterns are responsible for resistance to other HBV antiviral drugs.  ...  In HBV, treatment may fail due to the emergence of drug-resistant mutants.  ...  Nationale de la Recherche sur le SIDA et les hepatites virales' (ANRS CSS4 ECTZ25224-2017-19), the Institut Universitaire de France, LabEx CALSIMLAB (public grant ANR-11-LABX-0037-01 constituting a part of  ... 
doi:10.1093/ve/veaa006 pmid:32158552 pmcid:PMC7050494 fatcat:raqtzskcyrbyzjop22qjuqh3di

Genetic Consequences of Antiviral Therapy on HIV-1

Miguel Arenas
2015 Computational and Mathematical Methods in Medicine  
The role of recombination in the generation of drug resistance is also analyzed.  ...  Finally, the review discusses the importance of considering genetic consequences of antiviral therapies in models of HIV-1 evolution that could improve current genotypic resistance testing and treatments  ...  Moreover, antiviral therapies promote complex drug-specific residue-residue interaction networks [23, 70, 71] that can drive the coevolution of primary and secondary resistance mutations [8, 23] .  ... 
doi:10.1155/2015/395826 pmid:26170895 pmcid:PMC4478298 fatcat:wszymi7rv5d4zajqyfljab4pl4

COVTree: Coevolution in OVerlapped sequences by Tree analysis server

Elin Teppa, Diego J Zea, Francesco Oteri, Alessandra Carbone
2020 Nucleic Acids Research  
It is based on BIS2, a fast version of the coevolution analysis tool Blocks in Sequences (BIS).  ...  For these genes, molecular coevolution may be seen as a mechanism to decrease the evolutionary constraints of amino acid positions in the overlapping regions and to tolerate or compensate unfavorable mutations  ...  On the other hand, Pol is the target of antiviral therapy with nucleos(t)ide analogs. However, treatment may fail due to the emergence of drug-resistant mutants.  ... 
doi:10.1093/nar/gkaa330 pmid:32374885 fatcat:2px2n2haynes5i75x7kbdnzqha

Development of Web Application for the Comparison of Segment Variability with Sequence Evolution and Immunogenic Properties for Highly Variable Proteins: An Application to Viruses [article]

Sumit Bala, Ambarnil Ghosh, Subhra Pradhan
2021 bioRxiv   pre-print
High rate of mutation and structural flexibilities in viral proteins quickly make them resistant to the host immune system and existing antiviral strategies.  ...  Along with the experimental research related to antiviral development, computational data mining also plays an important role in deciphering the molecular and genomic signatures of the viral adaptability  ...  Novel mutations are the main reason behind inactivation of existing antiviral strategies.  ... 
doi:10.1101/2021.12.01.470810 fatcat:qnuvan4odff7xnh6cxk3crduju

Structural basis and distal effects of Gag substrate coevolution in drug resistance to HIV-1 protease

Ayşegül Özen, Kuan-Hung Lin, Nese Kurt Yilmaz, Celia A. Schiffer
2014 Proceedings of the National Academy of Sciences of the United States of America  
The authors declare no conflict of interest. This article is a PNAS Direct Submission.  ...  Fig. 1 . 1 HIV-1 protease and p1-p6 cleavage site coevolution with I50V primary drug resistance mutation.  ...  HIV-1 protease is a key antiviral drug target due to its essential function of processing Gag and Gag-Pol polyproteins in viral maturation (10) (11) (12) .  ... 
doi:10.1073/pnas.1414063111 pmid:25355911 pmcid:PMC4234576 fatcat:xej7mx5synd5fffoapzr4l3ppy

HIV-1 Protease and Substrate Coevolution Validates the Substrate Envelope As the Substrate Recognition Pattern

Ayşegül Özen, Türkan Haliloğlu, Celia A. Schiffer
2012 Journal of Chemical Theory and Computation  
To develop robust inhibitors targeting ensembles of drug-resistant variants, the code of this balance needs to be cracked.  ...  Drug resistance of HIV-1 protease alters the balance in the molecular recognition events in favor of substrate processing versus inhibitor binding.  ...  T.H. acknowledges DPT 2010K120670, Turkish Academy of Sciences (TUBA), and Betil Fund.  ... 
doi:10.1021/ct200668a pmid:24348205 pmcid:PMC3862175 fatcat:wnpwtoddprhshhwijsycihew44

Integrated Analysis of Residue Coevolution and Protein Structures Capture Key Protein Sectors in HIV-1 Proteins

Yuqi Zhao, Yanjie Wang, Yuedong Gao, Gonghua Li, Jingfei Huang, Yuxian He
2015 PLoS ONE  
These protein sectors are closely associated with anti-HIV drug resistance, T cell epitopes, and antibody binding sites.  ...  In this study, we examined patterns of sequence variability for evidence of linked sequence changes (termed as coevolution or covariation) in 15 HIV-1 proteins.  ...  At times, a single mutation in the genetic code can confer complete resistance to some antiviral drugs ( Table 3 ), suggesting that the transitions of amino acid do not perturb the functions of proteins  ... 
doi:10.1371/journal.pone.0117506 pmid:25671429 pmcid:PMC4324911 fatcat:ppbbfmvshzguxiweipvyyivgny

Convergence and coevolution of Hepatitis B virus drug resistance

Hong Thai, David S. Campo, James Lara, Zoya Dimitrova, Sumathi Ramachandran, Guoliang Xia, Lilia Ganova-Raeva, Chong-Gee Teo, Anna Lok, Yury Khudyakov
2012 Nature Communications  
The differential capacity of HBV variants to develop drug resistance suggests that fitness effects of drug-resistance mutations depend on the genetic structure of the HBV genome.  ...  Treatment with lamivudine of patients infected with hepatitis B virus (HBV) results in a high rate of drug resistance, which is primarily associated with the rtm204I/V substitution in the HBV reverse transcriptase  ...  ., C.T. and A.L contributed to discussion of results and provided critical reading of the manuscript; H.T., D.S.C., J.L. and Y.K. wrote the manuscript. Additional information  ... 
doi:10.1038/ncomms1794 pmid:22510694 pmcid:PMC3337990 fatcat:gcl5fa3i2fbhnpx3ricv6lu5sy

Coevolutionary analysis of resistance-evading peptidomimetic inhibitors of HIV-1 protease

C. D. Rosin, R. K. Belew, G. M. Morris, A. J. Olson, D. S. Goodsell
1999 Proceedings of the National Academy of Sciences of the United States of America  
For HIV-1 protease, typical drug design techniques are shown to be ineffective for the design of resistance-evading inhibitors: An inhibitor that is a direct analogue of one of the natural substrates will  ...  We have developed a coevolutionary method for the computational design of HIV-1 protease inhibitors selected for their ability to retain efficacy in the face of protease mutation.  ...  Effective methods to combat drug resistance are currently a field of intense study.  ... 
doi:10.1073/pnas.96.4.1369 pmid:9990030 pmcid:PMC15469 fatcat:gg4gax6q3bdklgvwmrop3xmdvq

Virus evolution

Peter Simmonds, Esteban Domingo
2011 Current Opinion in Virology  
Much of this work has been associated with the development of a variety of molecular biology and bioinformatic analysis techniques.  ...  Current research investigations range from evolutionary studies of virus variability and recombination, molecular epidemiology and investigations of viral pathogenesis and interactions of virus with host  ...  The almost systematic selection of viral mutants resistant either to single or multiple antiviral drugs is a firm observation in clinical practice.  ... 
doi:10.1016/j.coviro.2011.10.021 pmid:22440843 fatcat:xj4uloezobd55lvgb7zkcfjyh4

Facilitating Antiviral Drug Discovery Using Genetic and Evolutionary Knowledge

Xuan Xu, Qing-Ye Zhang, Xin-Yi Chu, Yuan Quan, Bo-Min Lv, Hong-Yu Zhang
2021 Viruses  
Since the virus mutation rate is much faster than that of the host, such drugs feature drug resistance and narrow-spectrum antiviral problems.  ...  Therefore, the targeting of host molecules has gradually become an important area of research for the development of antiviral drugs.  ...  This data can be found here: DrugBank (, accessed on 20 October 2021) and the SCG-Drug database (Quan et al. 2019).  ... 
doi:10.3390/v13112117 pmid:34834924 pmcid:PMC8626054 fatcat:dywpho3lqbfnhk57kit2wb65pa

Pathogen Mutation Modeled by Competition Between Site and Bond Percolation

Laurent Hébert-Dufresne, Oscar Patterson-Lomba, Georg M. Goerg, Benjamin M. Althouse
2013 Physical Review Letters  
We present mean-field and stochastic analysis of an epidemic model with antiviral administration and resistance development.  ...  While disease propagation is a main focus of network science, its coevolution with treatment has yet to be studied in this framework.  ...  LHD is grateful to the Natural Sciences and Engineering Research Council of Canada and to Calcul Québec for computing facilities.  ... 
doi:10.1103/physrevlett.110.108103 pmid:23521302 fatcat:bp5oz5ilfja5netai5oockwotq

General Mechanisms of Antiviral Resistance [chapter]

Anthony Vere Hodge, Hugh J. Field
2011 Genetics and Evolution of Infectious Disease  
While herpesvirus drug-resistance occurs at relatively high frequency in tissue culture, the widespread clinical use of herpesvirus antivirals is rarely limited by the emergence of resistance in immunocompetent  ...  of resistance to antiviral compounds and vaccines-the selection of random mutations.  ...  Cross References to Other Chapters (1) Molecular epidemiology and species definition of pathogens Michel Tibayrenc  ... 
doi:10.1016/b978-0-12-384890-1.00013-3 fatcat:zp6x5hjvjbhgfdbibhxlvradie

Drug-resistant HIV-1 protease regains functional dynamics through cleavage site coevolution

Nevra Özer, Ayşegül Özen, Celia A. Schiffer, Türkan Haliloğlu
2015 Evolutionary Applications  
Drug resistance is caused by mutations that change the balance of recognition favoring substrate cleavage over inhibitor binding.  ...  Overall, this study aids in the understanding of the structural dynamics basis of drug resistance and evolutionary optimization in the HIV-1 protease system.  ...  drug-resistant mechanism of HIV-1 protease.  ... 
doi:10.1111/eva.12241 pmid:25685193 pmcid:PMC4319865 fatcat:mbdszamzn5g2nhzktmmz5kxfce

Proteomic and phylogenetic coevolution analyses of pM79 and pM92 identify interactions with RNA polymerase II and delineate the murine cytomegalovirus late transcription complex

Travis J Chapa, Yushen Du, Ren Sun, Dong Yu, Anthony R French
2017 Journal of General Virology  
Combining proteomic methods with coevolution computational analysis provides novel insights into the relationship between pM79, pM92 and RNA polymerase II and allows the generation of a model of the multi-component  ...  We use inter-protein coevolution analysis to show how pM79 and pM92 likely assemble into a late transcription complex composed of late transcription regulators pM49, pM87 and pM95.  ...  Acknowledgements We thank Roger Everett (University of Glasgow) for the pLKO.DCMV.  ... 
doi:10.1099/jgv.0.000676 pmid:27926822 pmcid:PMC5903853 fatcat:4wjltvu6prb7zl7ze53oprffhu
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