scholarly journals Intracellular Life Cycle Kinetics of SARS-CoV-2 Predicted Using Mathematical Modelling

Viruses ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1735
Author(s):  
Dmitry Grebennikov ◽  
Ekaterina Kholodareva ◽  
Igor Sazonov ◽  
Antonina Karsonova ◽  
Andreas Meyerhans ◽  
...  
Keyword(s):  
Life Cycle ◽  
Drug Targets ◽  
Deterministic Model ◽  
Antiviral Drug ◽  
Computational Modelling ◽  
Structural Proteins ◽  
Model Parameters ◽  
Translation Rate ◽  
Infection Dynamics ◽  
Negative Effect

SARS-CoV-2 infection represents a global threat to human health. Various approaches were employed to reveal the pathogenetic mechanisms of COVID-19. Mathematical and computational modelling is a powerful tool to describe and analyze the infection dynamics in relation to a plethora of processes contributing to the observed disease phenotypes. In our study here, we formulate and calibrate a deterministic model of the SARS-CoV-2 life cycle. It provides a kinetic description of the major replication stages of SARS-CoV-2. Sensitivity analysis of the net viral progeny with respect to model parameters enables the identification of the life cycle stages that have the strongest impact on viral replication. These three most influential parameters are (i) degradation rate of positive sense vRNAs in cytoplasm (negative effect), (ii) threshold number of non-structural proteins enhancing vRNA transcription (negative effect), and (iii) translation rate of non-structural proteins (positive effect). The results of our analysis could be used for guiding the search for antiviral drug targets to combat SARS-CoV-2 infection.

Dengue Structural Proteins as Antiviral Drug Targets: Current Status in the Drug Discovery & Development

2021 ◽  
pp. 113527
Author(s):  
Akshatha H. S ◽  
Gurubasavaraj V. Pujar ◽  
Arun Kumar Sethu ◽  
Meduri Bhagyalalitha ◽  
Manisha Singh
Keyword(s):  
Drug Discovery ◽  
Drug Targets ◽  
Antiviral Drug ◽  
Structural Proteins ◽  
Current Status

Coronavirus Disease 2019: Virology and Drug Targets

2020 ◽  
Vol 20 ◽  
Author(s):  
Praveen Thaggikuppe Krishnamurthy
Keyword(s):  
High Throughput Screening ◽  
Drug Targets ◽  
Vaccine Development ◽  
Antiviral Drug ◽  
Drug Repurposing ◽  
Structural Proteins ◽  
Current Status ◽  
Approved Drugs ◽  
Viral Target ◽  
Fda Approved Drugs

: The Coronavirus Disease 2019, a pandemic caused by novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), is seriously affecting global health and the economy. As the vaccine development takes time, the current research is focused on repurposing FDA approved drugs against the viral target proteins. This review discusses the current understanding of SARS-CoV-2 virology, its target structural proteins (S- glycoprotein), non-structural proteins (3- chymotrypsin-like protease, papain-like protease, RNA-dependent RNA polymerase, and helicase) and accessory proteins, drug discovery strategies (drug repurposing, artificial intelligence, and high-throughput screening), and the current status of antiviral drug development.

Covid 19 – Structural proteins and prospective drug candidates (Preprint)

2020 ◽  
Author(s):  
A.N Anoopkumar ◽  
Sharrel Rebello ◽  
Embalil Mathachan Aneesh
Keyword(s):  
Causative Agent ◽  
Protein Level ◽  
Drug Targets ◽  
Current Paper ◽  
Structural Proteins ◽  
Drug Candidates ◽  
Propagation Properties

UNSTRUCTURED Covid 19 the causative agent of the current devastating pandemic has turned out to be a notorious virus to all men-irrespective of either common to scientific calibre. Attempts to combat this deadly virus are the need of the hour and quite often the best way to defeat an opponent is to keenly study about its structural and propagation properties. The current paper describes briefly Covid 19 at the genomic, structural and protein level to the best of our knowledge. Furthermore, the prospects of possible drug targets that could aid in the control of this virus are also discussed.

scholarly journals Network-Guided Discovery of Influenza Virus Replication Host Factors

mBio ◽  
2018 ◽  
Vol 9 (6) ◽  
Author(s):  
Emily E. Ackerman ◽  
Eiryo Kawakami ◽  
Manami Katoh ◽  
Tokiko Watanabe ◽  
Shinji Watanabe ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Viral Replication ◽  
Virus Replication ◽  
Drug Targets ◽  
Antiviral Drug ◽  
Viral Proteins ◽  
Host Factors ◽  
Ppi Network ◽  
Host Proteins ◽  
Influenza Virus Replication

ABSTRACTThe positions of host factors required for viral replication within a human protein-protein interaction (PPI) network can be exploited to identify drug targets that are robust to drug-mediated selective pressure. Host factors can physically interact with viral proteins, be a component of virus-regulated pathways (where proteins do not interact with viral proteins), or be required for viral replication but unregulated by viruses. Here, we demonstrate a method of combining human PPI networks with virus-host PPI data to improve antiviral drug discovery for influenza viruses by identifying target host proteins. Analysis shows that influenza virus proteins physically interact with host proteins in network positions significant for information flow, even after the removal of known abundance-degree bias within PPI data. We have isolated a subnetwork of the human PPI network that connects virus-interacting host proteins to host factors that are important for influenza virus replication without physically interacting with viral proteins. The subnetwork is enriched for signaling and immune processes distinct from those associated with virus-interacting proteins. Selecting proteins based on subnetwork topology, we performed an siRNA screen to determine whether the subnetwork was enriched for virus replication host factors and whether network position within the subnetwork offers an advantage in prioritization of drug targets to control influenza virus replication. We found that the subnetwork is highly enriched for target host proteins—more so than the set of host factors that physically interact with viral proteins. Our findings demonstrate that network positions are a powerful predictor to guide antiviral drug candidate prioritization.IMPORTANCEIntegrating virus-host interactions with host protein-protein interactions, we have created a method using these established network practices to identify host factors (i.e., proteins) that are likely candidates for antiviral drug targeting. We demonstrate that interaction cascades between host proteins that directly interact with viral proteins and host factors that are important to influenza virus replication are enriched for signaling and immune processes. Additionally, we show that host proteins that interact with viral proteins are in network locations of power. Finally, we demonstrate a new network methodology to predict novel host factors and validate predictions with an siRNA screen. Our results show that integrating virus-host proteins interactions is useful in the identification of antiviral drug target candidates.

scholarly journals Analysis of a mosquito life cycle model

2021 ◽  
Vol Volume 34 - 2020 - Special... ◽  
Author(s):  
Albert Kouchéré ◽  
Hamadjam Abboubakar ◽  
Irepran Damakoa
Keyword(s):  
Life Cycle ◽  
Sterile Insect Technique ◽  
Deterministic Model ◽  
Communicable Disease ◽  
Control Measures ◽  
Reproductive Number ◽  
Gonotrophic Cycle ◽  
Complete Life Cycle ◽  
Trivial Equilibrium ◽  
International Audience

International audience The gonotrophic cycle of mosquitoes conditions the frequency of mosquito-human contacts. The knowledge of this important phenomenon in the mosquito life cycle is a fundamental element in the epidemiological analysis of a communicable disease such as mosquito-borne diseases.In this work, we analyze a deterministic model of the complete life cycle of mosquitoes which takes into account the principal phases of female mosquitoes' gonotrophic cycle, and the Sterile Insect technique combined with the use of insecticide as control measures to fight the proliferation of mosquitoes. We compute the corresponding mosquito reproductive number N ∗ and prove the global asymptotic stability of trivial equilibrium. We prove that the model admits two non-trivial equilibria whenever N^{∗} is greater than another threshold, N_c, which the total number of sterile mosquitoes depends on. Numerical simulations, using mosquito parameters of the Aedes species, are carried out to illustrate our analytical results and permit to show that the strategy which consists in combining the sterile insect technique with adulticides, when it is well done, effectively combats the proliferation of mosquitoes.

scholarly journals Sex-Associated Differences in Cytomegalovirus Prevention: Prophylactic Strategy is Potentially Associated With a Strong Kidney Function Impairment in Female Renal Transplant Patients

2020 ◽  
Vol 11 ◽  
Author(s):  
Arturo Blazquez-Navarro ◽  
Chantip Dang-Heine ◽  
Chris Bauer ◽  
Nicole Wittenbrink ◽  
Kerstin Wolk ◽  
...  
Keyword(s):  
Strong Association ◽  
Antiviral Drug ◽  
Bk Virus ◽  
Virus Reactivation ◽  
Post Transplantation ◽  
Female Patients ◽  
Viral Loads ◽  
Transplant Patients ◽  
Randomized Controlled Studies ◽  
Negative Effect

Post-transplantation cytomegalovirus (CMV) syndrome can be prevented using the antiviral drug (val)ganciclovir. (Val)ganciclovir is typically administered following a prophylactic or a pre-emptive strategy. The prophylactic strategy entails early universal administration, the pre-emptive strategy, early treatment in case of infection. However, it is not clear which strategy is superior with respect to transplantation outcome; sex-specific effects of these prevention strategies are not known. We have retrospectively analyzed 540 patients from the multi-centre Harmony study along eight pre-defined visits: 308 were treated according to a prophylactic, 232 according to a pre-emptive strategy. As expected, we observed an association of prophylactic strategy with lower incidence of CMV syndrome, delayed onset and lower viral loads compared to the pre-emptive strategy. However, in female patients, the prophylactic strategy was associated with a strong impairment of glomerular filtration rate one year post-transplant (difference: −11.8 ± 4.3 ml min−1·1.73 m−2, p = 0.006). Additionally, we observed a tendency of higher incidence of acute rejection and severe BK virus reactivation in the prophylactic strategy group. While the prophylactic strategy was more effective for preventing CMV syndrome, our results suggest for the first time that the prophylactic strategy might lead to inferior transplantation outcomes in female patients, providing evidence for a strong association with sex. Further randomized controlled studies are necessary to confirm this potential negative effect.

scholarly journals Helicases as antiviral drug targets

2003 ◽  
Vol 16 (6) ◽  
pp. 355 ◽  
Author(s):  
D.N. Frick
Keyword(s):  
Drug Targets ◽  
Antiviral Drug

scholarly journals Modeling infection dynamics and mitigation strategies to support K-6 in-person instruction during the COVID-19 pandemic

2021 ◽  
Author(s):  
Douglas E. Morrison ◽  
Roch Nianogo ◽  
Vladimir Manuel ◽  
Onyebuchi A. Arah ◽  
Nathaniel Anderson ◽  
...  
Keyword(s):  
School Attendance ◽  
Secondary Infection ◽  
Mitigation Strategies ◽  
Transmission Dynamics ◽  
Model Parameters ◽  
Safety Education ◽  
Vaccination Rates ◽  
Health Authorities ◽  
Infection Dynamics ◽  
Public Health Authorities

AbstractObjectiveTo support safer in-person K-6 instruction during the coronavirus disease 2019 (COVID- 19) pandemic by providing public health authorities and school districts with a practical model of transmission dynamics and mitigation strategies.MethodsWe developed an agent-based model of infection dynamics and preventive mitigation strategies such as distancing, health behaviors, surveillance and symptomatic testing, daily symptom and exposure screening, quarantine policies, and vaccination. The model parameters can be updated as the science evolves and are adjustable via an online user interface, enabling users to explore the effects of interventions on outcomes of interest to states and localities, under a variety of plausible epidemiological and policy assumptions.ResultsUnder default assumptions, secondary infection rates and school attendance are substantially affected by surveillance testing protocols, vaccination rates, class sizes, and effectiveness of safety education.ConclusionsOur model helps policymakers consider how mitigation options and the dynamics of school infection risks affect outcomes of interest. The model’s parameters can be immediately updated in response to changes in epidemiological conditions, science of COVID-19 transmission dynamics, testing and vaccination resources, and reliability of mitigation strategies.

A GENERAL SOFTWARE TESTING MODEL INVOLVING OPERATIONAL PROFILES

2001 ◽  
Vol 15 (4) ◽  
pp. 519-533 ◽  
Author(s):  
Süleyman Özekici ◽  
I. Kuban Altinel ◽  
Ebru Angün
Keyword(s):  
Nonlinear Programming ◽  
Convex Optimization ◽  
Deterministic Model ◽  
Failure Process ◽  
Testing Procedure ◽  
Model Parameters ◽  
Programming Formulation ◽  
Testing Model ◽  
Operational Profile ◽  
Software Testing Model

An operational profile describes, in a probabilistic way, how a software is utilized by its users. It makes the testing procedure more realistic and efficient. We consider a model where the software is tested sequentially in all of the operations that it is designed to perform. The stochastic and deterministic model parameters involving costs and failures all depend on the operations. In particular, the failure process generated by each fault is quite general and debugging is not necessarily perfect. Our aim is to find the optimal testing durations in all of the operations in order to minimize the total expected cost. This problem leads to an interesting nonlinear programming formulation that can be solved using well-known procedures in convex optimization.

scholarly journals Modeling the Effects of Spatial Heterogeneity and Seasonality on Guinea Worm Disease Transmission

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Anthony A. E. Losio ◽  
Steady Mushayabasa
Keyword(s):  
Spatial Heterogeneity ◽  
Vector Control ◽  
Disease Transmission ◽  
Disease Surveillance ◽  
Neglected Tropical Diseases ◽  
South Sudan ◽  
Model Parameters ◽  
Guinea Worm ◽  
Infection Dynamics ◽  
And Control

Guinea worm disease is one of the neglected tropical diseases that is on the verge of elimination. Currently the disease is endemic in four countries, namely, Ethiopia, Mali, Chad, and South Sudan. Prior studies have demonstrated that climate factors and limited access to safe drinking water have a significant impact on transmission and control of Guinea worm disease. In this paper, we present a new mathematical model to understand the transmission dynamics of Guinea worm disease in South Sudan. The model incorporates seasonal variations, educational campaigns, and spatial heterogeneity. Both qualitative and quantitative analysis of the model have been carried out. Utilizing Guinea worm disease surveillance data of South Sudan (2007-2013) we estimate the model parameters. Meanwhile, we perform an optimal control study to evaluate the implications of vector control on long-term Guinea worm infection dynamics. Our results demonstrate that vector control could play a significant role on Guinea worm disease eradication.

Sign in / Sign up

Export Citation Format

Share Document