Viral Kinetics of the Y448H HCV NS5B Polymerase Mutant in Patients Treated with the HCV Inhibitor Tegobuvir (GS-9190)

2013 ◽  
Vol 05 (04) ◽  
Author(s):  
Evguenia S Svarovskaia
Keyword(s):  
Viral Kinetics ◽  
Hcv Ns5b ◽  
Kinetics Of ◽  
Ns5b Polymerase

scholarly journals Mathematical analysis of a within-host model of SARS-CoV-2

2021 ◽  
Vol 2021 (1) ◽  
Author(s):  
Bhagya Jyoti Nath ◽  
Kaushik Dehingia ◽  
Vishnu Narayan Mishra ◽  
Yu-Ming Chu ◽  
Hemanta Kumar Sarmah
Keyword(s):  
Stability Analysis ◽  
Basic Reproduction Number ◽  
Reproduction Number ◽  
Basic Reproduction Ratio ◽  
Viral Kinetics ◽  
Reproduction Ratio ◽  
Biological Implication ◽  
Infection Models ◽  
Kinetics Of ◽  
The Basic Reproduction Number

AbstractIn this paper, we have mathematically analyzed a within-host model of SARS-CoV-2 which is used by Li et al. in the paper “The within-host viral kinetics of SARS-CoV-2” published in (Math. Biosci. Eng. 17(4):2853–2861, 2020). Important properties of the model, like nonnegativity of solutions and their boundedness, are established. Also, we have calculated the basic reproduction number which is an important parameter in the infection models. From stability analysis of the model, it is found that stability of the biologically feasible steady states are determined by the basic reproduction number $(\chi _{0})$ ( χ 0 ) . Numerical simulations are done in order to substantiate analytical results. A biological implication from this study is that a COVID-19 patient with less than one basic reproduction ratio can automatically recover from the infection.

scholarly journals Molecular modeling study on the drug resistance mechanism of NS5B polymerase to TMC647055

2016 ◽  
Vol 94 (2) ◽  
pp. 147-158 ◽  
Author(s):  
Huiqun Wang ◽  
Wei Cui ◽  
Chenchen Guo ◽  
Bo-Zhen Chen ◽  
Mingjuan Ji
Keyword(s):  
Drug Resistance ◽  
Free Energy ◽  
Rational Design ◽  
Binding Free Energy ◽  
Resistance Mechanism ◽  
Free Energy Calculations ◽  
Side Chain ◽  
Free Energy Decomposition ◽  
Hcv Ns5b ◽  
Ns5b Polymerase

NS5B polymerase plays an important role in viral replication machinery. TMC647055 (TMC) is a novel and potent non-nucleoside inhibitor of the HCV NS5B polymerase. However, mutations that result in drug resistance to TMC have been reported. In this study, we used molecular dynamics (MD) simulations, binding free energy calculations, and free energy decomposition to investigate the drug resistance mechanism of HCV to TMC resulting from L392I, P495T, P495S, and P495L mutations in NS5B polymerase. From the calculated results we determined that the decrease in the binding affinity between TMC and NS5BL392I polymerase is mainly caused by the extra methyl group at the CB atom of Ile. The polarity of the side-chain of residue 495 has no distinct influence on residue 495 binding with TMC, whereas the smaller size of the side-chain of residue 495 causes a substantial decrease in the van der Walls interaction between TMC and residue 495. Moreover, the longer length of the side-chain of residue 495 has a significant effect on the electrostatic interaction between TMC and Arg-503. Finally, we performed the same calculations and detailed analysis on other 3 mutations (L392V, P495V, and P495I). The results further confirmed our conclusions. The computational results not only reveal the drug resistance mechanism between TMC647055 and NS5B polymerase, but also provide valuable information for the rational design of more potent non-nucleoside inhibitors targeting HCV NS5B polymerase.

No influence of antiretroviral therapy on the mutation rate of the HCV NS5B polymerase in HIV/HCV-coinfected patients

2012 ◽  
Vol 95 (2) ◽  
pp. 67-71 ◽  
Author(s):  
Federico Alejandro Di Lello ◽  
Juan Macias ◽  
Zulema Plaza ◽  
Silvia García-Rey ◽  
Vicente Soriano ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Mutation Rate ◽  
Hcv Ns5b ◽  
Ns5b Polymerase

scholarly journals Discovery of N-Arylalkyl-3-hydroxy-4-oxo-3,4-dihydroquinazolin-2-carboxamide Derivatives as HCV NS5B Polymerase Inhibitors

ChemMedChem ◽  
2012 ◽  
Vol 7 (5) ◽  
pp. 850-860 ◽  
Author(s):  
Ravindra Ramesh Deore ◽  
Grace Shiahuy Chen ◽  
Pei-Teh Chang ◽  
Ting-Rong Chern ◽  
Shin-Yu Lai ◽  
...  
Keyword(s):  
Polymerase Inhibitors ◽  
Hcv Ns5b ◽  
Ns5b Polymerase

Allosteric N-acetamide-indole-6-carboxylic acid thumb pocket 1 inhibitors of hepatitis C virus NS5B polymerase — Acylsulfonamides and acylsulfamides as carboxylic acid replacements

2013 ◽  
Vol 91 (1) ◽  
pp. 66-81 ◽  
Author(s):  
Pierre L. Beaulieu ◽  
René Coulombe ◽  
James Gillard ◽  
Christian Brochu ◽  
Jianmin Duan ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Carboxylic Acid ◽  
Allosteric Inhibitors ◽  
Subgenomic Replicon ◽  
Structure Activity ◽  
Hcv Ns5b ◽  
Acid Function ◽  
Ns5b Polymerase

Acylsulfonamide and acylsulfamide as surrogates for the carboxylic acid function of N-acetamide-indole-6-carboxylic acids were evaluated as allosteric inhibitors of hepatitis C virus (HCV) NS5B polymerase. Several analogs displayed excellent antiviral potency against both 1a and 1b HCV genotypes in cell-based subgenomic replicon assays. Structure–activity relationships (SAR) are discussed in the context of the crystal structure of an inhibitor − NS5B polymerase complex. Absorption, distribution, metabolism, and excretion pharmacokinetic (ADME-PK) properties of this class of inhibitors are also described.

I. Novel HCV NS5B polymerase inhibitors: Discovery of indole 2-carboxylic acids with C3-heterocycles

2011 ◽  
Vol 21 (18) ◽  
pp. 5336-5341 ◽  
Author(s):  
Gopinadhan N. Anilkumar ◽  
Charles A. Lesburg ◽  
Oleg Selyutin ◽  
Stuart B. Rosenblum ◽  
Qingbei Zeng ◽  
...  
Keyword(s):  
Carboxylic Acids ◽  
Polymerase Inhibitors ◽  
Hcv Ns5b ◽  
Ns5b Polymerase

scholarly journals Simulation Model for Dynamics of Dengue with Innate and Humoral Immune Responses

2018 ◽  
Vol 2018 ◽  
pp. 1-18 ◽  
Author(s):  
S. D. Perera ◽  
S. S. N. Perera
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Dengue Virus ◽  
Dengue Infection ◽  
Asymptomatic Infection ◽  
Severe Dengue ◽  
Viral Kinetics ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Kinetics Of

Dengue virus is a mosquito borne Flavivirus and the most prevalent arbovirus in tropical and subtropical regions around the world. The incidence of dengue has increased drastically over the last few years at an alarming rate. The clinical manifestation of dengue ranges from asymptomatic infection to severe dengue. Even though the viral kinetics of dengue infection is lacking, innate immune response and humoral immune response are thought to play a major role in controlling the virus count. Here, we developed a computer simulation mathematical model including both innate and adaptive immune responses to study the within-host dynamics of dengue virus infection. A sensitivity analysis was carried out to identify key parameters that would contribute towards severe dengue. A detailed stability analysis was carried out to identify relevant range of parameters that contributes to different outcomes of the infection. This study provides a qualitative understanding of the biological factors that can explain the viral kinetics during a dengue infection.

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