Virus Diseases Commons^™

Modelling Acute Haemorrhagic Conjunctivitis In East Africa: An Integrated Approach To Transmission Dynamics And Outbreak Response Strategies, Geofrey Wingi Sikazwe

Tanzania Journal of Science

Acute hemorrhagic conjunctivitis (AHC) poses a significant global health risk, with the potential for rapid spread during outbreaks. For instance, a localized outbreak in Yunnan Province, China, recorded infection rates of up to 48%, illustrating how transmission can intensify under favourable epidemiological and environmental conditions. Existing mathematical models of AHC transmission overlook seasonal variations, a critical factor in epidemic spread. This study combines species distribution models (SDMs) and epidemiological modelling to analyse key drivers of AHC in East Africa. We use the SEIR type (Susceptible-Exposed-Infected-Recovered - incorporating waning immunity) framework with temperature-dependent infectivity rate as the key driver of an …

A Novel Mathematical Model Of Hiv Transmission Incorporating The Effects Of Treatment And Pre-Exposure Prophylaxis: Sensitivity Analysis And Numerical Simulations, Erick Manuel Delgado Moya

Mathematical Modelling and Numerical Simulation with Applications

Human immunodeficiency virus (HIV) continues to be a public health problem in many countries of the world, and Pre-exposure prophylaxis (PrEP) is a preventive method for HIV, which has shown great efficacy and is in use worldwide. This work presents a new mathematical model for HIV transmission incorporating PrEP use and evaluates the impact of PrEP along with its increasing use in a population. The construction of the model takes into account three forms of diagnosis: diagnosis of individuals in risky sexual contact, diagnosis after risky contact (diagnosis in the undiagnosed infected compartment), and diagnosis associated with attempting to enter …

Mathematical Analysis And Numerical Simulation Of A Fractional-Order Sir-Si Model For Malaria Transmission Dynamics, Gassan A. M. O. Farah, Abdulaziz Y. A. Mukhtar, Kailash C. Patidar

Mathematical Modelling and Numerical Simulation with Applications

This study investigates the complex transmission dynamics of malaria, a critical global health challenge, with a focus on the African continent. We introduce a novel approach that employs Fractional Differential Equations (FDEs) to advance the understanding of malaria spread and control. Specifically, we develop a new SIR-SI model using the Caputo fractional operator, which captures the memory effects and time-delay characteristics inherent in real-world epidemiological systems. A detailed analysis of the model's solvability and uniqueness is conducted using fixed-point theory. To obtain an analytical solution, the system is solved via the Laplace transform method, with solutions expressed in closed form …

Allosteric Control Overcomes Steric Limitations For Neutralizing Antibodies Targeting Conserved Binding Epitopes Of The Sars-Cov-2 Spike Protein: Exploring The Intersection Of Binding, Allostery, And Immune Escape With A Multimodal Computational Approach, Mohammed Alshahrani, Vedant Parikh, Brandon Foley, Gennady M. Verkhivker

Mathematics, Physics, and Computer Science Faculty Articles and Research

Understanding the atomistic basis of multi-layer mechanisms employed by broadly reactive neutralizing antibodies of the SARS-CoV-2 spike protein without directly blocking receptor engagement remains an important challenge in coronavirus immunology. Class 4 antibodies represent an intriguing case: they target a deeply conserved, cryptic epitope on the receptor-binding domain yet exhibit variable neutralization potency across subgroups F1 (CR3022, EY6A, COVA1-16), F2 (DH1047), and F3 (S2X259). The molecular basis for this variability is not fully understood. Here, we employed a multi-modal computational approach integrating atomistic and coarse-grained molecular dynamics simulations, binding free energy calculations, mutational scanning, and dynamic network analysis to elucidate …

Dynamic Mutational Profiling Of Binding Interactions And Allosteric Networks In Conformational Ensembles Of The Sars-Cov-2 Spike Protein Complexes With Classes Of Antibodies Targeting Cryptic Binding Sites: Confluence Of Binding And Allostery Determines Molecular Mechanisms And Hotspots Of Immune Escape, Mohammed Alshahrani, Vedant Parikh, Brandon Foley, Gennady M. Verkhivker

Mathematics, Physics, and Computer Science Faculty Articles and Research

The ongoing evolution of SARS-CoV-2 variants has underscored the need to understand not only the structural basis of antibody recognition but also the dynamic and allosteric mechanisms that could underlie complexity of broad and escape-resistant neutralization. In this study, we employed a multi-scale approach integrating structural analysis, hierarchical molecular simulations, mutational scanning and network-based allosteric modeling to dissect how Class 4 antibodies (represented by S2X35, 25F9, and SA55) and Class 5 antibodies (represented by S2H97, WRAIR-2063 and WRAIR-2134) can modulate conformational behavior, binding energetics, allosteric interactions and immune escape patterns of the SARS-CoV-2 spike protein. Using hierarchical simulations of the …

Multiscale Modeling And Dynamic Mutational Profiling Of Binding Energetics And Immune Escape For Class I Antibodies With Sars-Cov-2 Spike Protein: Dissecting Mechanisms Of High Resistance To Viral Escape Against Emerging Variants, Mohammed Alshahrani, Vedant Parikh, Brandon Foley, Gennady M. Verkhivker

Mathematics, Physics, and Computer Science Faculty Articles and Research

The rapid evolution of SARS-CoV-2 has underscored the need for a detailed understanding of antibody binding mechanisms to combat immune evasion by emerging variants. In this study, we investigated the interactions between Class I neutralizing antibodies—BD55-1205, BD-604, OMI-42, P5S-1H1, and P5S-2B10—and the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein using multiscale modeling, which combined molecular simulations with the ensemble-based mutational scanning of the binding interfaces and binding free energy computations. A central theme emerging from this work is that the unique binding strength and resilience to immune escape of the BD55-1205 antibody are determined by leveraging a broad epitope …

Utilization Of Flow Cytometry, Metabolomic Analyses And A Feline Infectious Peritonitis Case Study To Evaluate The Physiological Impact Of Polyprenyl Immunostimulant, Irene Lee, Amar Desai, Akshay Patil, Yan Xu, Kelley Pozza-Adams, Anthony J. Berdis

Chemistry Faculty Publications

Measles, hepatitis C, and COVID-19 are significant human diseases caused by RNA viruses. While vaccines exist to prevent infections, there are a small number of currently available therapeutic agents that can effectively treat these diseases after infection occurs. This study explores a new therapeutic strategy using a small molecule designated polyprenyl immunostimulant (PI) to increase innate immune responses and combat viral infections. Using a multi-disciplinary approach, this study quantifies the effects of PI in mice and THP-1 cells using flow cytometry to identify immune phenotypic markers and mass spectroscopy to monitor the metabolomic profiles of immune cells perturbed by PI …

The Effects Of Climate Change On The Advancement Of West Nile Virus, Mackenzie R. Epperson

ATU Scholars Symposium

The West Nile virus (WNV) first emerged in the United States in the year 1999 within the state of New York and has become endemic throughout the country over time. This virus is contracted from an avian species acting as the reservoir host, by the vector species which are mosquitoes. From this point, the mosquitoes transmit the virus to humans and other mammals, which are the dead end hosts. The WNV often presents itself as flu-like symptoms, but in serious cases can cause severe arboviral neurological disease. Since this is an arbovirus, it is important to have the ability to …

Mutational Scanning And Binding Free Energy Computations Of The Sars-Cov-2 Spike Complexes With Distinct Groups Of Neutralizing Antibodies: Energetic Drivers Of Convergent Evolution Of Binding Affinity And Immune Escape Hotspots, Mohammed Alshahrani, Vedant Parikh, Brandon Foley, Nishank Raisinghani, Gennady M. Verkhivker

Mathematics, Physics, and Computer Science Faculty Articles and Research

The rapid evolution of SARS-CoV-2 has led to the emergence of variants with increased immune evasion capabilities, posing significant challenges to antibody-based therapeutics and vaccines. In this study, we conducted a comprehensive structural and energetic analysis of SARS-CoV-2 spike receptor-binding domain (RBD) complexes with neutralizing antibodies from four distinct groups (A–D), including group A LY-CoV016, group B AZD8895 and REGN10933, group C LY-CoV555, and group D antibodies AZD1061, REGN10987, and LY-CoV1404. Using coarse-grained simplified simulation models, rapid energy-based mutational scanning, and rigorous MM-GBSA binding free energy calculations, we elucidated the molecular mechanisms of antibody binding and escape mechanisms, identified key …

Quantitative Characterization And Prediction Of The Binding Determinants And Immune Escape Hotspots For Groups Of Broadly Neutralizing Antibodies Against Omicron Variants: Atomistic Modeling Of The Sars-Cov-2 Spike Complexes With Antibodies, Mohammed Alshahrani, Vedant Parikh, Brandon Foley, Nishank Raisinghani, Gennady M. Verkhivker

Mathematics, Physics, and Computer Science Faculty Articles and Research

A growing body of experimental and computational studies suggests that the cross-neutralization antibody activity against Omicron variants may be driven by the balance and tradeoff between multiple energetic factors and interaction contributions of the evolving escape hotspots involved in antigenic drift and convergent evolution. However, the dynamic and energetic details quantifying the balance and contribution of these factors, particularly the balancing nature of specific interactions formed by antibodies with epitope residues, remain largely uncharacterized. In this study, we performed molecular dynamics simulations, an ensemble-based deep mutational scanning of SARS-CoV-2 spike residues, and binding free energy computations for two distinct groups …

Estimating Per-Infection Cost And Burden For Dengue And Zika As A Function Of Antibody-Dependent Enhancement, Christopher M. Kribs

Mathematics Faculty Publications - Archive

The complex immune interactions produced by the tetravalent dengue vaccine Dengvaxia have foregrounded the important role of antibody-dependent enhancement (ADE) in dengue infection. Some evidence exists that ADE may extend beyond the four dengue serotypes to Zika, a closely related flavivirus transmitted by the same mosquito species as dengue, and may also account for the increased severity of some cases. Estimates of the public health impact of dengue vaccination may then need to include its effects on the transmission of Zika in addition to dengue. This study gathers primary references to build estimates of per-case economic cost and disease burden …

Asymmetric Synthesis Of The Hiv Protease Inhibitor Tmc-126 And An Anti-Malarial Agent Via A Titanium Tetrachloride Mediated Asymmetric Glycolate Aldol Addition Reaction. Redefining The Curtius Rearrangement Reaction Via Dehomologation Of Carboxylic Acids Bearing Alpha-Leaving Groups, Kweku Amaning Affram

Theses and Dissertations

Acquired Immune Deficiency Syndrome (AIDS) and malaria are two devastating infectious diseases caused by HIV and Plasmodium parasites. AIDS is caused by HIV-1 and HIV-2, transmitted through sexual contact, blood transfusions, needle sharing, and perinatal routes. Malaria, caused by plasmodium parasites through mosquito bites. Today, millions of people around the world have been infected with HIV and malaria and much research has been done to treat it. However, despite advancements in therapeutic options, these diseases remain a significant global health threat, particularly in developing countries due to the emergence of drug-resistant strains for both HIV and malaria complicating eradication efforts. …

Alphafold2 Modeling And Molecular Dynamics Simulations Of The Conformational Ensembles For The Sars-Cov-2 Spike Omicron Jn.1, Kp.2 And Kp.3 Variants: Mutational Profiling Of Binding Energetics Reveals Epistatic Drivers Of The Ace2 Affinity And Escape Hotspots Of Antibody Resistance, Nishank Raisinghani, Mohammed Alshahrani, Grace Gupta, Gennady M. Verkhivker

Mathematics, Physics, and Computer Science Faculty Articles and Research

AlphaFold2-based atomistic predictions of structures and conformational ensembles of the SARS-CoV-2 spike complexes with the host receptor ACE2 for the most dominant Omicron variants JN.1, KP.1, KP.2 and KP.3 to examine the mechanisms underlying the role of convergent evolution hotspots in balancing ACE2 binding and antibody evasion. Using the ensemble-based mutational scanning of the spike protein residues and computations of binding affinities, we identified binding energy hotspots and characterized the molecular basis underlying epistatic couplings between convergent mutational hotspots. The results suggested the existence of epistatic interactions between convergent mutational sites at L455, F456, Q493 positions that protect and restore …

Cucumber Mosaic Virus And Its Management In Narrow Leafed Lupins, Department Of Primary Industries And Regional Development, Western Australia

Grains and other field crops factsheets

Cucumber mosaic virus (CMV) is a seed- and aphid-borne virus that infects narrow-leafed lupins. Western Australian (WA) grainbelt regions most at risk are the high rainfall zones of the northern and central agricultural region and the south coastal region.

The principal infection source for lupin crops is sowing infected lupin seed.

Foliar Diseases And Their Management In Lupins, Department Of Primary Industries And Regional Development, Western Australia

Grains and other field crops factsheets

This factsheet describes symptoms and management of the major fungal and viral diseases affecting lupin foliage, stems, and pods. Several of these diseases have the capacity to cause significant losses if not managed effectively.

Inoculum can be carried in soil, seed, stubble, on green regrowth, or by insect vectors, depending on the disease. Therefore, an integrated approach to disease management is required using tactics such as crop rotation, stubble management, fungicide seed dressing, variety selection, and seed testing

Information Feedback Delays Within Epidemic Models And Their Effect On Model Dynamics., Maria K. Bouka, Christopher Strickland Dr

Biology and Medicine Through Mathematics Conference

No abstract provided.

Exploring Binding Pockets In The Conformational States Of The Sars-Cov-2 Spike Trimers For The Screening Of Allosteric Inhibitors Using Molecular Simulations And Ensemble-Based Ligand Docking, Grace Gupta, Gennady M. Verkhivker

Mathematics, Physics, and Computer Science Faculty Articles and Research

Understanding mechanisms of allosteric regulation remains elusive for the SARS-CoV-2 spike protein, despite the increasing interest and effort in discovering allosteric inhibitors of the viral activity and interactions with the host receptor ACE2. The challenges of discovering allosteric modulators of the SARS-CoV-2 spike proteins are associated with the diversity of cryptic allosteric sites and complex molecular mechanisms that can be employed by allosteric ligands, including the alteration of the conformational equilibrium of spike protein and preferential stabilization of specific functional states. In the current study, we combine conformational dynamics analysis of distinct forms of the full-length spike protein trimers and …

In Silico Analysis Of C-Type Lectins As Co-Infection Receptors Of Dengue And Chikungunya Viruses In Aedes Aegypti, Munawir Sazali, R. C. Hidayat Soesilohadi, Nastiti Wijayanti, Tri Wibawa, Arif Nur Muhammad Ansori

Makara Journal of Science

Aedes aegypti is a primer vector of dengue virus (DENV) and chikungunya virus (CHIKV). The susceptibility of mosquitoes to DENV and CHIKV depends on their recognition receptor of pathogens. C-type lectins (CTLs) are an important mediator of virus infection in A. aegypti. This study aims to identify potential receptors and determine the binding affinity between ligand–receptor interaction, CTLs and virus envelopes (DENV-1, 2, 3, and 4 and CHIKV) interaction based on in silico analysis. Sample sequences were obtained from GenBank (NCBI), and 10 CTLs were acquired from VectorBase. Homology modeling based on a minimum standard of 20% was processed …

A Tale Of Two Viruses: Why Smallpox Was Eradicated And Polio Persists, Katherine G. Mcgough, Erin N. Bodine

Spora: A Journal of Biomathematics

The smallpox and poliomyelitis (polio) viruses were, at a time, one of the largest threats to global public health killing millions until global eradication campaigns were put into effect. Vaccination led to the eradication of smallpox and the elimination of polio for most of the world. However, polio continues to persist at endemic levels in Pakistan and Afghanistan. We developed ODE models of smallpox and polio to explore differences in transmission dynamics and determine if the underlying biology has made poliomyelitis more difficult to eradicate. Our model analysis shows there are multiple factors which should allow polio to have a …

Raman Spectroscopic Analysis Of Human Serum Samples Of Convalescing Covid-19 Positive Patients, Hugh Byrne, Naomi Jackson, Jaythoon Hassan

Articles

Rapid screening, detection and monitoring of viral infection is of critical importance, as exemplified by the rapid spread of SARS-CoV-2, leading to the worldwide pandemic of COVID-19. This is equally the case for the stages of patient convalescence as for the initial stages of infection, to understand the medium and long terms effects, as well as the efficacy of therapeutic interventions. Optical spectroscopic techniques potentially offer an alternative to currently employed techniques of screening for the presence, or the response to infection. In this study, the ability of Raman spectroscopy to distinguish between samples of the serum of convalescent COVID-19 …

Long-Acting Cabotegravir And The Emergence Of Drug-Resistant Hiv, Katharine Gurski

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

Predicting Dengue Incidence In Central Argentina Using Google Trends Data, Sahil Chindal

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

Assessment Of First-Phase Covid-19 Pandemic In Europe Using Hierarchical Clustering Based On Principal Components Analysis, Sanjay Kumar, Evrim Oral

School of Public Health Faculty Publications

It is of great interest for researchers to assess the COVID-19 pandemic in Europe. Grouping of COVID-19-affected regions is an effective way to monitor and optimize planning to combat the disease. This paper applied hierarchical clustering based on principal components analysis (HCPCA) to COVID-19 data from affected European countries. Considering several attribute indices, we obtained a new set of indicators using principal components analysis to aggregate and reduce the dimension of attribute indices of affected countries. Further, we obtained groups of affected countries subject to their similarity using hierarchical clustering to the reduced observations of new attributes indices of these …

Climate Change, Malnutrition, And Hiv: The Impact Of Food Insecurity On Hiv Response In Sub-Saharan Africa, Olivia Walshak

Independent Study Project (ISP) Collection

Climate change is a key driver of an unprecedented global food crisis, exacerbated by rising temperatures and the vulnerability of crop yields. Sub-Saharan Africa is particularly susceptible, and case studies demonstrate the fragility of food systems in the region, leading to severe food insecurity and famine in the face of climate shocks.

There are a variety of health implications, particularly the syndemic relationship between malnutrition and HIV. HIV interacts bidirectionally with malnutrition, creating a vicious cycle of poor clinical outcomes. Expanding access to antiretroviral therapy in Sub-Saharan Africa is hindered by rampant food insecurity, including inadequate food intake, reduced dietary …

Probing Conformational Landscapes Of Binding And Allostery In The Sars-Cov-2 Omicron Variant Complexes Using Microsecond Atomistic Simulations And Perturbation-Based Profiling Approaches: Hidden Role Of Omicron Mutations As Modulators Of Allosteric Signaling And Epistatic Relationships, Gennady M. Verkhivker, Mohammed Alshahrani, Grace Gupta, Sian Xiao, Peng Tao

Mathematics, Physics, and Computer Science Faculty Articles and Research

In this study, we systematically examine the conformational dynamics, binding and allosteric communications in the Omicron BA.1, BA.2, BA.3 and BA.4/BA.5 spike protein complexes with the ACE2 host receptor using molecular dynamics simulations and perturbation-based network profiling approaches. Microsecond atomistic simulations provided a detailed characterization of the conformational landscapes and revealed the increased thermodynamic stabilization of the BA.2 variant which can be contrasted with the BA.4/BA.5 variants inducing a significant mobility of the complexes. Using the dynamics-based mutational scanning of spike residues, we identified structural stability and binding affinity hotspots in the Omicron complexes. Perturbation response scanning and network-based mutational …

Metals And Metal Complexes In Diseases With A Focus On Covid-19: Facts And Opinions, Agnieszka Ścibior, Manuel Aureliano, Alvin A. Holder, Juan Llopis

Chemistry & Biochemistry Faculty Publications

In the present Special Issue on “Metals and Metal Complexes in Diseases with a Focus on COVID-19: Facts and Opinions”, an attempt has been made to include reports updating our knowledge of elements considered to be potential candidates for therapeutic applications and certain metal-containing species, which are extensively being examined towards their potential biomedical use due to their specific physicochemical properties. The Special Issue compiles data on the role of metals in COVID-19 and focuses on other illnesses and biological processes that affect metal metabolism. It consists of eight manuscripts, including five review articles and three original research papers (Figure …

Balancing Functional Tradeoffs Between Protein Stability And Ace2 Binding In The Sars-Cov-2 Omicron Ba.2, Ba.2.75 And Xbb Lineages: Dynamics-Based Network Models Reveal Epistatic Effects Modulating Compensatory Dynamic And Energetic Changes, Gennady M. Verkhivker, Mohammed Alshahrani, Grace Gupta

Mathematics, Physics, and Computer Science Faculty Articles and Research

Evolutionary and functional studies suggested that the emergence of the Omicron variants can be determined by multiple fitness trade-offs including the immune escape, binding affinity for ACE2, conformational plasticity, protein stability and allosteric modulation. In this study, we systematically characterize conformational dynamics, structural stability and binding affinities of the SARS-CoV-2 Spike Omicron complexes with the host receptor ACE2 for BA.2, BA.2.75, XBB.1 and XBB.1.5 variants. We combined multiscale molecular simulations and dynamic analysis of allosteric interactions together with the ensemble-based mutational scanning of the protein residues and network modeling of epistatic interactions. This multifaceted computational study characterized molecular mechanisms and …

An Investigation On The Effect Of Conserved Hinge Histidine On Influenza Hemagglutinin(Ha2) Protein Conformation Using Md Simulations, Nada Tolba

Chemistry & Biochemistry Undergraduate Honors Theses

Hemagglutinin is a protein on the surface of Human Influenza Viruses.¹ It is composed of two glycopolypeptide domains, the HA1 and HA2 domains. Previous studies have found that across different strains of Influenza viruses, HIS435 residues remain conserved.⁴ In studies where mutations occurred in hinge-site histadine residues, the Influenza virus was inactive.⁴ These investigations indicated a significant role of HIS435 (hinge-site histadines) in virulence. Four systems were created using Molecular dynamics (MD) simulations. Each system was composed of an Isolated HA2 trimer solvated in a 150 mM NaCl rectangular water box at 310 K under isobaric and …

Coarse-Grained Molecular Simulations And Ensemble-Based Mutational Profiling Of Protein Stability In The Different Functional Forms Of The Sars-Cov-2 Spike Trimers: Balancing Stability And Adaptability In Ba.1, Ba.2 And Ba.2.75 Variants, Gennady M. Verkhivker, Mohammed Alshahrani, Grace Gupta

Mathematics, Physics, and Computer Science Faculty Articles and Research

Evolutionary and functional studies have suggested that the emergence of Omicron variants can be determined by multiple fitness tradeoffs including immune escape, binding affinity, conformational plasticity, protein stability, and allosteric modulation. In this study, we embarked on a systematic comparative analysis of the conformational dynamics, electrostatics, protein stability, and allostery in the different functional states of spike trimers for BA.1, BA.2, and BA.2.75 variants. Using efficient and accurate coarse-grained simulations and atomistic reconstruction of the ensembles, we examined the conformational dynamics of the spike trimers that agree with the recent functional studies, suggesting that BA.2.75 trimers are the most stable …

Modeling Immune System Dynamics During Hiv Infection And Treatment With Differential Equations, Nicole Rychagov

CODEE Journal

An inquiry-based project that discusses immune system dynamics during HIV infection using differential equations is presented. The complex interactions between healthy T-cells, latently infected T-cells, actively infected T-cells, and the HIV virus are modeled using four nonlinear differential equations. The model is adapted to simulate long term HIV dynamics, including the AIDS state, and is used to simulate the long term effects of the traditional antiretroviral therapy (ART). The model is also used to test viral rebound over time of combined application of ART and a new drug that blocks the reactivation of the viral genome in the infected cells …