Viruses Commons^™

Ns5-Targeting Nucleoside Analogs Inhibit Dengue Virus And Other Flaviviruses, Priyanka Bhakt, Swechha Pokharel, Yue Li, Tamanna Srivastava, Jesse Miller, Mark Dittmar, Yongqing Zhu, David Nguyen, Zachary Walter, Kasirajan Ayyanathan, Matthew Tudor, Chenguang Yu, Arnab Chatterjee, Holly Ramage, David Schultz, Sara Cherry

Department of Microbiology and Immunology Faculty Papers

Dengue virus (DENV) is a mosquito-transmitted flavivirus that circulates globally as four distinct serotypes and poses a substantial threat to public health. There are an estimated ~96 million symptomatic infections yearly, including severe cases of dengue fever, underscoring the urgency of identifying effective therapeutics targeting all four serotypes. Nucleoside analogs, which mimic endogenous nucleosides to inhibit viral RNA replication, offer a promising strategy for broad-spectrum antiviral development. Here, we conducted a high-throughput screen of 1,101 nucleoside analogs against DENV serotype 2 (DENV2) in a panel of human cell models, including human epithelial cells, hepatocytes, and fibroblasts. Candidates that were active …

Surveillance Of A Novel Vesivirus Discovered In An Urban Mephitis Mephitis Population, Amanda E. Diggins

Honors Theses and Capstones

Caliciviridae is a family of non-enveloped, positive-sense, single stranded RNA viruses, including eleven defined genera that contain important pathogens of humans and animals. Within the Caliciviridae family, the genus Vesiviridae includes feline calicivirus, a leading cause of upper respiratory disease in cats, and vesicular exanthema of swine virus, a historical disease of domestic swine that has now been implicated in several marine mammal vesicular diseases, one of which has been confirmed zoonotic. Urban landscapes create a unique environment for rapid intra- and interspecies transmission of viruses. Clustered resources attract high-density populations of synanthropic wildlife species, increasing spatial overlap and heightening …

Increasing Pediatric Hpv Vaccination Rates, Brooke A. Nicholas

Dissertations

Increasing Pediatric HPV Vaccination Rates

Abstract

Problem: The human papillomavirus (HPV) is a sexually transmitted infection that affects more than 80% of the population within the United States (Eisenhauer et al., 2020). HPV can develop into cervical, anogenital, and oropharyngeal cancers (Eisenhauer et al., 2020). About 4,000 individuals die from cervical cancer alone each year (O’Leary, 2022). The HPV vaccine, though recommended by the ACIP and AAP, is below national vaccination rates in comparison to other vaccines (O’Leary, 2022).

Methods: This quality improvement project is a non-randomized controlled trial that observed HPV vaccine dose completion rates for patients aged 9-14 …

Development Of A Multi-Epitope Peptide Vaccine Against Monkeypox Virus: Immunoinformatics Analysis For South East Asian Hla Alleles, Nelson Chandra, Mochammad Aqilah Herdiansyah, Viol Dhea Kharisma, Arif Nur Muhammad Ansori, Arli Aditya Parikesit

Makara Journal of Science

The monkeypox virus (MPXV), a DNA virus causing zoonotic disease, poses major global public health challenges, with mortality rates between 3%–6%. Although smallpox vaccines provide partial cross-protection, there is a critical need for a dedicated, effective monkeypox (mpox) vaccine. This study aimed to design a multi-epitope peptide-based vaccine specifically adapted to the HLA allele profiles common in Southeast Asian populations, where MPXV cases are rising. Using immunoinformatics, we screened for and detected B and T cell epitopes from the MPXV cell surface antigen and IFN-alpha/beta receptor proteins. The vaccine design was validated through a rigorous evaluation of its antigenicity, immunogenicity, …

Synthesis And Evaluation Of Anti-Hiv Activity Of Fatty Acyl Conjugates Of Tenofovir Alefanamide, Muhammad Sajid, Naglaa Salem El-Sayed, Louise A. Ouattara, Amita Verma, Gustavo F. Doncel, Keykavous Parang, M. Iqbal Choudhary, Hina Siddiqui

CONRAD Publications

The activity of nucleoside and nucleotide analogs as antiviral agents requires phosphorylation by intracellular enzymes. Phosphate-substituted analogs have low bioavailability due to the presence of ionizable negatively-charged groups. To circumvent this limitation, several prodrug approaches have been proposed and developed. Herein, we hypothesized that the conjugation of anti-HIV fatty acids with the nucleotide tenofovir alafenamide (TAF) (1) could improve the anti-HIV activity of the nucleotide. Several fatty acyl amide conjugates of TAF were synthesized and evaluated in comparative studies with TAF. The synthesized compounds were evaluated as racemic mixtures for anti-HIV activity in vitro in a single-round HIV-1 infection assay …

Identification Of Benzothiophene-Derived Inhibitors Of Flaviviruses By Targeting Rna-Dependent Rna Polymerase, Leah Liu Wang, Shazeed-Ul Karim, Aidan Hand, Ryan Brunkhorst, Mackenna Petersen, Sarah Altam, Yi Liu, Luwen Zhang, Fengwei Bai, Shi-Hua Xiang

School of Biological Sciences: Faculty Publications

Flaviviruses such as Dengue, West Nile, and Zika viruses are mosquito-borne RNA viruses that can cause serious diseases in humans. To develop effective drugs for treating these viruses’ infections, we create a new approach for developing common or shared drugs that may work for several different viral species of flaviviruses. It is based on the conserved RNA-dependent RNA polymerase (RdRp), which is the key enzyme for viral replication. We built up a common structure of RdRps (POLcon) from their consensus sequence. A conserved Triple-D structural motif was identified at the active site of POLcon that has been used for virtual …

The Importance Of Solution Studies For The Structural Characterization Of The Enterovirus 5' Cloverleaf, Morgan G. Daniels, Meagan E. Werner, Xiaobing Zuo, Steven M. Pascal

Chemistry & Biochemistry Faculty Publications

Enteroviruses initiate genomic replication via a highly conserved mechanism that is controlled by an RNA platform, also known as the 5' cloverleaf (5'CL). Here, we present a biophysical analysis of the 5'CL conformation of three enterovirus serotypes under various ionic conditions, utilizing CD spectroscopy, size-exclusion chromatography, and small-angle X-ray scattering. In general, a tendency toward a smaller monomeric hydrodynamic radius in the presence of salts was observed, but the exact structural signature of each 5'CL varied depending upon the serotype. Rhinovirus B14 (RVB14) exhibited at least two monomeric conformations and a low propensity for dimerization, while poliovirus 1 (PV1) showed …

Dengue Virus Modulates Critical Cell Cycle Regulatory Proteins In Human Megakaryocyte Cells, Swarnendu Basak, Shovan Dutta, Supreet Khanal, Girish Neelakanta, Hameeda Sultana

Biological Sciences Faculty Publications

Suppression of human megakaryocytes by dengue virus (DENV) infection significantly reduces the platelet count that eventually leads to thrombocytopenia, severe dengue and death. To understand DENV interactions with megakaryocytes, we investigated the cell cycle in leukemic human megakaryocytic in vitro cell line (MEG-01 cells). Megakaryocytes are known for complex endomitotic cell cycle leading to their polyploidy state. Our study shows that DENV uses these polyploid cells for its replication. Understanding the modulation of DENV-mediated cell cycle regulation in megakaryocytes is therefore highly important. We show that DENV2 (serotype 2) infection significantly modulates cell cycle signaling. Our protein profile microarray data …

Viral Genome Delivery Across Bacterial Cell Surfaces, Stephano M. Iglesias, Fenglin Li, Federica Briani, Gino Cingolani

Department of Biochemistry and Molecular Biology Faculty Papers

In 1952, Hershey and Chase used bacteriophage T2 genome delivery inside Escherichia coli to demonstrate that DNA, not protein, is the genetic material. Over 70 years later, our understanding of bacteriophage structure has grown dramatically, mainly thanks to the cryogenic electron microscopy revolution. In stark contrast, phage genome delivery in prokaryotes remains poorly understood, mainly due to the inherent challenge of studying such a transient and complex process. Here, we review the current literature on viral genome delivery across bacterial cell surfaces. We focus on icosahedral bacterial viruses that we arbitrarily sort into three groups based on the presence and …

Cryo-Em Analysis Of Pseudomonas Phage Pa193 Structural Components, Stephano M. Iglesias, Chun-Feng Hou, Johnny Reid, Evan Schauer, Renae Geier, Angela Soriaga, Lucy Sim, Lucy Gao, Julian Whitelegge, Pierre Kyme, Deborah Birx, Sebastien Lemire, Gino Cingolani

Department of Biochemistry and Molecular Biology Faculty Papers

The World Health Organization has designated Pseudomonas aeruginosa as a critical pathogen for the development of new antimicrobials. Bacterial viruses, or bacteriophages, have been used in various clinical settings, commonly called phage therapy, to address this growing public health crisis. Here, we describe a high-resolution structural atlas of a therapeutic, contractile-tailed Pseudomonas phage, Pa193. We used bioinformatics, proteomics, and cryogenic electron microscopy single particle analysis to identify, annotate, and build atomic models for 21 distinct structural polypeptide chains forming the icosahedral capsid, neck, contractile tail, and baseplate. We identified a putative scaffolding protein stabilizing the interior of the capsid 5-fold …

Developing Coexpression Systems To Introduce Hydroxyproline Into Protein Engineered Collagen Peptides Utilizing Hydroxylase From Acanthamoeba Polyphaga Mimivirus, Jennifer Soldatich

Theses and Dissertations

A major challenge of developing collagen mimetic peptides (CMPs) by bacterial expression is to include hydroxyproline for biomedical applications. Coexpression of Prolyl-4-hydroxylase from A.mimivirus with CMPs was investigated. Additionally, four expression designs were created for potential applications in mammalian cells to utilize their natural ability of proline-hydroxylation by post-translational modification.

Bean Yellow Mosaic Virus And Its Management In Lupins, Department Of Primary Industries And Regional Development, Western Australia

Grains and other field crops factsheets

Bean yellow mosaic virus (BYMV) is an aphid-transmitted virus that commonly causes necrotic symptoms that kills lupin plants when infected early before pod set. When plants are infected after pod set, black pods develop (known as black pod syndrome).

BYMV is found predominantly in high rainfall areas of the Western Australian (WA) grainbelt. This page outlines the symptoms, diagnosis, factors favouring disease risk and spread, yield and quality impacts, and management for BYMV in lupin crops in WA

Barley And Cereal Yellow Dwarf Viruses And Their Management, Department Of Primary Industries And Regional Development, Western Australia

Grains and other field crops factsheets

Barley yellow dwarf viruses (BYDV) and cereal yellow dwarf viruses (CYDV) damage cereal crops worldwide. These yellow dwarf viruses infect wheat, barley, oats and grasses and are transmitted by aphids.

This page describes these collective yellow dwarf viruses (barley and cereal yellow dwarf viruses), which damage cereals crops and advises on their diagnosis, monitoring, and management the viruses in the Western Australian (WA) grainbelt.

Growers are encouraged to check cereal crops for aphids on a regular basis, especially early in the season during autumn when winged aphids migrate into cereal crops during the crops’ most vulnerable growth phase. Early detection …

Managing Aphids And Viruses In Lupins, Department Of Primary Industries And Regional Development, Western Australia

Grains and other field crops factsheets

Aphids reduce yields by direct feeding damage, which causes flower and pod abortion and occasionally plant death in lupins. The extent of damage varies between seasons, but losses can be severe in years that favour aphid population development.

Lupins are most vulnerable to aphids during budding and flowering, as severe feeding damage on growing tips can cause buds to drop, flowers to abort, and reduced pod set. Some lupin varieties are more susceptible to aphids than others.

Aphids transmit serious virus diseases, which reduce yields and contaminate seed stocks. Some species of aphids are more difficult to control than others.

Motif-Vi Loop Acts As A Nucleotide Valve In The West Nile Virus Ns3 Helicase, Priti Roy, Zachary Walter, Lauren Berish, Holly Ramage, Martin Mccullagh

Department of Microbiology and Immunology Faculty Papers

The Orthoflavivirus NS3 helicase (NS3h) is crucial in virus replication, representing a potential drug target for pathogenesis. NS3h utilizes nucleotide triphosphate (ATP) for hydrolysis energy to translocate on single-stranded nucleic acids, which is an important step in the unwinding of double-stranded nucleic acids. Intermediate states along the ATP hydrolysis cycle and conformational changes between these states, represent important yet difficult-to-identify targets for potential inhibitors. Extensive molecular dynamics simulations of West Nile virus NS3h+ssRNA in the apo, ATP, ADP+Pi and ADP bound states were used to model the conformational ensembles along this cycle. Energetic and structural clustering analyses depict a clear …

Triticale As A Source Of Resistance To Wheat Streak Mosaic Virus And Triticum Mosaic Virus, Marcos Winicius Goncalves De Souza

Department of Agronomy and Horticulture: Dissertations, Theses, and Student Research

Wheat streak mosaic virus (WSMV) and Triticum mosaic virus (TriMV) present a great threat to wheat production in the Great Plains area of the United States due to the loss of photosynthetic area causing reductions in crop yields. Effective control of these viruses is limited to a few available strategies including controlling volunteer wheat and using currently identified resistant genes to both the vector and viruses. While effective, these genes show temperature sensitivity and yield drag, and evidence that the vectors and viruses can overcome them has been found. Thus, new methods of genetic resistance are urgently needed. Field observations …

Delivering Crispr To The Hiv-1 Reservoirs, Theodore Gurrola, Samuel Effah, Ilker Sariyer, Will Dampier, Michael Nonnemacher, Brian Wigdahl

Kimmel Cancer Center Faculty Papers

Human immunodeficiency virus type 1 (HIV-1) infection is well known as one of the most complex and difficult viral infections to cure. The difficulty in developing curative strategies arises in large part from the development of latent viral reservoirs (LVRs) within anatomical and cellular compartments of a host. The clustered regularly interspaced short palindromic repeats/ CRISPR-associated protein 9 (CRISPR/Cas9) system shows remarkable potential for the inactivation and/or elimination of integrated proviral DNA within host cells, however, delivery of the CRISPR/Cas9 system to infected cells is still a challenge. In this review, the main factors impacting delivery, the challenges for delivery …

Exploration Of Potential Broad-Spectrum Antiviral Targets In The Enterovirus Replication Element: Identification Of Six Distinct 5' Cloverleaves, Morgan G. Daniels, Meagan E. Werner, Rockwell T. Li, Steven M. Pascal

Chemistry & Biochemistry Faculty Publications

Enterovirus genomic replication initiates at a predicted RNA cloverleaf (5′CL) at the 5′ end of the RNA genome. The 5′CL contains one stem (SA) and three stem-loops (SLB, SLC, SLD). Here, we present an analysis of 5′CL conservation and divergence for 209 human health-related serotypes from the enterovirus genus, including enterovirus and rhinovirus species. Phylogenetic analysis indicates six distinct 5′CL serotypes that only partially correlate with the species definition. Additional findings include that 5′CL sequence conservation is higher between the EV species than between the RV species, the 5′CL of EVA and EVB are nearly identical, and RVC has the …

Harnessing Antagonistic Pleiotropy: Tolc-Dependent Coliphages Can Drive Reduced Antibiotic Resistance In E. Coli, Cooper Mckenna

CMC Senior Theses

The rise of multidrug-resistant (MDR) bacterial pathogens has been a growing concern in healthcare around the world, and bacteriophage (phage) therapy is a promising method to combat MDR infections. One defense mechanism of E. coli against antibiotics is the TolC-AcrAB efflux pump. At the same time, some phages use TolC as a surface receptor to infect the cell. This puts TolC at a crossroads in which it is beneficial to the bacteria to protect against antibiotics but harmful by allowing phage infection, creating the potential for evolutionary trade-offs. Previous research has identified only three TolC-dependent phages and shown phage-resistant E. …

Tim/Tam Receptors: A Potential Biomarker For Predicting Sensitivity To Zika Virus-Induced Oncolysis In Non-Small Cell Lung Cancers, Shankari Somasekar

Honors Undergraduate Theses

Non-small cell lung cancers (NSCLC) constitute 80-85% of lung cancers and are the leading cause of cancer-related deaths globally. The most common cause is prolonged smoking. Current treatment options for NSCLC include surgery, radiation, chemotherapy, targeted drug therapy, and immunotherapy. Although these medications are effective in the short term, patients often face issues of drug resistance and debilitating side effects with prolonged use. Currently, the use of Zika virus (ZIKV) is being researched as a possible alternative treatment for cancer, which minimizes side effects and the risk of drug resistance. TIM/TAM proteins are identified as the putative ZIKV receptors on …

The Developmental Process For Adenoviral Vectored Canine Influenza Vaccines, Nicholas Jeanjaquet

School of Biological Sciences: Dissertations, Theses, and Student Research

Canine Influenza Virus (CIV) is a recently emerged branch of Influenza A virus that is highly infectious in dogs. The first strain was isolated in 2003, and it has quickly become endemic in areas with dense dog populations, most notably in Asia. The proximity of dogs to humans, along with their potential to serve as mixing vessels for reassortment, raises concern for possible zoonotic transmission and a potential human pandemic. Available vaccines are not frequently updated and struggle to prevent the spread of currently circulating strains. This highlights the need for a new and more effective vaccine. We outline the …

Analyzing Pseudomonas Aeruginosa With Bacteriophage Tags Using Photoacoustic Flow Cytometry, Jennifer C. Schinke

Electronic Theses and Dissertations

The number of daily bacterial infections is climbing and the CDC explains that this is due to the antibiotic-resistant threat in the United States. Finding a faster way of bacterial identification is necessary as it currently takes 1-4 days for a medical lab to culture and identify bacteria. Photoacoustic flow cytometry (PAFC) can be used as an alternative method resulting in swift identification within an hour (Edgar, 2019). Pseudomonas aeruginosa, cell line PA01, will be coated in up to a few hundred red dyed phages making it detectible by the photoacoustic flow cytometry system. Bacteriophages (phages) are viruses that …

An Overview Of Viruses And The Infamous Sars-Cov-2, Jake Sun

The Confluence

Background information on viruses is first presented which include topics like evolution, ecology, history, identification, structure, and application. The novel SARS-CoV-2, which causes COVID-19, pandemic originated in Wuhan, China in December 2019. Millions of people were infected with the virus in a short time period causing urgent concern worldwide. The purpose of this review is to provide a brief and general understanding of the SARS-CoV-2 to increase awareness and actions toward preventive measures. COVID-19 is a (+) ssRNA spherical enveloped virion that causes primarily respiratory illnesses. The S protein interacts with ACE-2 receptors on the host cell to gain entry …

Prevalence Of Sars-Cov-2 Antibodies In Liberty University Student Population, Emily Bonus

Senior Honors Theses

In 2020, the virus SARS-CoV-2 gained attention as it spread around the world. Its antibodies are poorly understood, and little research focuses on those with few COVID-19 complications yet large numbers of close contacts: university students. This longitudinal study recorded SARS-CoV-2 antibody presence in 107 undergraduate Liberty University students twice during early 2021. After extensive data cleaning and the application of various statistical tests and ANOVAs, the data seems to show that in the case of COVID-19 infections, SARS-CoV-2 IgM antibodies are immediately produced, and then IgG antibodies follow later. However, the COVID-19 vaccine causes the production of both IgM …

Promiscuous Feeding Across Multiple Honey Bee Hosts Amplifies The Vectorial Capacity Of Varroa Destructor, Zachary S. Lamas, Serhat Solmaz, Eugene V. Ryabov, Joseph Mowery, Matthew Heermann, Daniel Sonenshine, Jay D. Evans, David J. Hawthorne

Biological Sciences Faculty Publications

Varroa destructor is a cosmopolitan pest and leading cause of colony loss of the European honey bee. Historically described as a competent vector of honey bee viruses, this arthropod vector is the cause of a global pandemic of Deformed wing virus, now endemic in honeybee populations in all Varroa-infested regions. Our work shows that viral spread is driven by Varroa actively switching from one adult bee to another as they feed. Assays using fluorescent microspheres were used to indicate the movement of fluids in both directions between host and vector when Varroa feed. Therefore, Varroa could be in either …

Proposing An Rna Interference (Rnai)-Based Treatment For Human Immunodeficiency Virus (Hiv) By Analyzing The Post-Transcriptional Gene Targeting Of Sars-Cov-2, Hepatitis C Virus, And A549 Lung Cancer Cells, Arjun Jagdeesh

Undergraduate Research Posters

Human Immunodeficiency Virus (HIV) is a retrovirus that infects CD4+ T cell lymphocytes in humans, leading to the development of Acquired Immunodeficiency Syndrome (AIDS) if left untreated. While current treatment methods, including antiretroviral combination treatments, effectively limit HIV replication, HIV can evade these treatments due to its high mutation rate. Long-term antiretroviral treatment can also be toxic to patients, meaning patients would benefit from a new mechanism of HIV treatment. RNA interference (RNAi) is an antiviral pathway found in mammals, plants, and insects that involves a small-interfering RNA that is incorporated into a protein complex called the RNA-induced Silencing Complex …

Electrochemical Inactivation Of Tobacco Mosaic Virus: A Novel Vaccine Method, Angelica Diaz

Undergraduate Research Symposium Posters

We tested the effectiveness of using electrochemistry to irreversibly damage Tobacco Mosaic Virus (TMV). Hypothesis: By utilizing the acidic properties of DNA and RNA, viral genetic material can be irreversibly and selectively damaged using electrochemical methods. Technique could assist in development of highly targeted and effective vaccines.

Sea-Phages Research Opportunity, Sarah Ballarin

Trick to the Treat of Internships and Research

Research opportunity targeted for freshmen and sophomores through the SEA-PHAGES program. The goal of the research is to discover new bacteriophages (viruses that infect bacteria) to help combat antibiotic resistance. Phage therapy is a promising alternative to conventional antibiotics. Phages have also been widely used in the food industry to prevent microbial growth on certain foods and are currently being explored as a method for bioremediation of oil spills and wastewater treatment.

Last year, my research team discovered two new bacteriophages: Genamy16 and NovaSharks that were able to infect the bacteria Gordonia rubripertincta. These phages can possibly be used for …

The Sars-Cov-2 Differential Genomic Adaptation In Response To Varying Uvindex Reveals Potential Genomic Resources For Better Covid-19 Diagnosis And Prevention, Naveed Iqbal, Muhammad Rafiq, Masooma Ali, Sanaullah Tareen, Maqsood Ahmad, Faheem Nawaz, Sumair Khan, Rida Riaz, Ting Yang, Ambrin Fatima

Department of Biological & Biomedical Sciences

Coronavirus disease 2019 (COVID-19) has been a pandemic disease reported in almost every country and causes life-threatening, severe respiratory symptoms. Recent studies showed that various environmental selection pressures challenge the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infectivity and, in response, the virus engenders new mutations, leading to the emergence of more virulent strains of WHO concern. Advance prediction of the forthcoming virulent SARS-CoV-2 strains in response to the principal environmental selection pressures like temperature and solar UV radiation is indispensable to overcome COVID-19. To discover the UV-solar radiation-driven genomic adaption of SARS-CoV-2, a curated dataset of 2,500 full-grade genomes from …

Microplastics In Freshly Fallen Snow: How May It Adversely Impact Human Health And Exacerbate The Covid-19 Crisis?, Ayesha Liaquat, Aleena Kashif, Sushma Rathi, Alishba Raza

Medical College Documents

No abstract provided.