Viruses Commons^™

Comparison Of Ecg Features, Cardiac Biomarkers, And Clinical Outcomes In Three Waves Of Hospitalized Covid-19 Pneumonia Patients With Cardiovascular Events, Yuchen Han, Jahnavi Sunkara, Tshura S Ali, Harideep Samanapally, Vidyulata Salunkhe, Fnu Deepti, Emma C. Huang, Justin J. Huang, Maiying Kong, Jiapeng Huang

The University of Louisville Journal of Respiratory Infections

Background

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is a rapidly evolving virus that can severely impact the cardiovascular system. With new variants, it is important to characterize wave-specific (defined by dominant circulating variants) clinical changes.

Methods

A multi-center retrospective cohort study of patients hospitalized with SARS-CoV-2 community acquired pneumonia at eight adult acute-care hospitals in the city of Louisville, KY was conducted. Patients hospitalized with Coronavirus Disease 2019 (COVID-19) community acquired pneumonia who experienced a cardiovascular event between March 2020 and July 2022 were included in this analysis. Variant assignment was based on temporal prevalence rather than genomic confirmation, and …

Metabolic And Replicative Constraints On Pathogen Virulence: Isoleucine Catabolism In Shigella And Comparative Tanapoxvirus Replication In Cell Cultures, Benecia Angelica

Masters Theses

Pathogens survive by balancing metabolic demands with environmental challenges that shape their virulence and adaptability. Shigella flexneri, a highly infectious human pathogen responsible for severe diarrheal disease worldwide, utilizes branched-chain amino acid (BCAA) metabolism to withstand stress conditions encountered within the host environment. In this study, we explored the Shigella isoleucine catabolism pathway by knocking out four genes in the S. flexneri isoleucine catabolic pathway (ilvE, fadA, fadD, and acnB) and examining their metabolism and virulence. We found that the ilvE and acnB mutants displayed reduced metabolic activity and smaller plaque size, while the fadD mutant showed decreased invasion. In …

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 …

Aggressive Natural Killer Cell Leukemia: A Rare And Rapidly Progressive Hematologic Malignancy—Case Report And Literature Review, Jennifer Priessnitz, Ali Hariri, Yuliya Levkiavska, Kyle E. Bonner, Stephan I. Fisher, Joshua M. Sill

Department of Medicine Faculty Publications

Aggressive natural killer cell leukemia (ANKL) is a rare, fulminant hematologic malignancy characterized by neoplastic proliferation of mature NK cells. It is frequently associated with Epstein-Barr virus (EBV) infection, although EBV-negative cases have also been reported. While typically observed in young to middle-aged adults of East Asian descent, increasing recognition has led to identification of ANKL across diverse age groups and ethnicities. The disease is defined by a rapid clinical course and poor prognosis, underscoring the importance of early diagnosis and effective treatment. We present a case of a 71-year-old Caucasian male who developed fever, altered mental status, hepatosplenomegaly, pancytopenia, …

Presenteeism Among Health Care Personnel With Covid-19, James C. Crosby, Eliezer Santos Leon, Brian Chinnock, Karisa K. Harland, Anusha Krishnadasan, Nicholas M. Mohr, Ian D. Plumb, Melissa Briggs Hagen, Kelli Wallace, David A. Talan, Project Prevent Network, Anne Zepeski, Tracy Young, Howard A. Smithline, Lilly C. Lee, Stephen C. Lim, Et Al

School of Medicine Faculty Publications

IMPORTANCE: Presenteeism-defined as continuing to work during an illness-poses a public health risk in the workplace and is especially hazardous within health care institutions where vulnerable patients may be exposed to nosocomial infections. Understanding the frequency and characteristics of health care personnel (HCP) who report presenteeism while ill with COVID-19 may help mitigate SARS-CoV-2 spread in hospitals and other health care institutions. OBJECTIVES: To determine the frequency of presenteeism among HCP with symptomatic COVID-19, and to evaluate the demographic, occupational, and clinical factors associated with it. DESIGN, SETTING, AND PARTICIPANTS: This is an observational cohort study that uses data from …

Adaptive Compulsion, Amanda A. Santos

Electronic Theses, Projects, and Dissertations

Adaptive

Adjective

Adap.tive ( ə-ˈdap-tiv)

of, relating to, or being a heritable trait that serves a specific function and improves an organism's fitness or survival

Compulsion

Noun

Com.pul.sion (kəm-ˈpəl-shən)

a repetitive behavior or mental act that a person feels driven to perform to alleviate the anxiety and distress caused by an unwanted thought or urge, known as an obsession.

For years we have lived in unprecedented times. From the worldwide quarantine in 2020 resulting from the pandemic, to our current US political crisis. The constant barrage of events is overwhelming and demoralizing.

The work in this gallery is a display …

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 …

Transcriptomic And Epigenomic Profiling Of Immune Cells Responses To Simian Immunodeficiency Virus Infection In The Brain, Xiaoke Xu

Theses & Dissertations

Human immunodeficiency virus type 1 (HIV-1) is an enveloped retrovirus that significantly impairs the human immune system. A common complication of HIV-1 infection is HIV-associated neurocognitive disorder (HAND), which, prior to the introduction of antiretroviral therapy (ART), led to considerable morbidity and mortality due to untreated neuropsychiatric manifestations. Although ART has substantially reduced the incidence of HIV-associated dementia (HAD), approximately 50% of people living with HIV (PLWH) continue to experience milder forms of HAND. The CNS is seeded by HIV during the acute phase of infection. Once in the brain, HIV targets and activates resident immune cells, primarily microglia and …

Current Trends In Clinical Trials For Merkel Cell Carcinoma (Mcc), Tilak Patel, Rachel Butz, Brian Boulmay, Vilija Vaitaitis

School of Medicine Faculty Publications

Merkel cell carcinoma (MCC) is a rare, aggressive neuroendocrine cutaneous malignancy with high rates of recurrence and metastasis. The treatment of MCC has historically involved surgery, radiation, and chemotherapy; however, current clinical trials are investigating immunotherapies, intratumoral injections, and combination therapies to improve outcomes. This review explores the current trends in clinical trials for MCC, highlighting recent advances in management.

Comprehensive Resolution And Classification Of The Epstein Barr Virus Transcriptome, Truong D. Nguyen, Jia Wang, Meggie T. Lam, Harris Mcferrin, Tina M. O’Grady, Claire Roberts, Nicholas Van Otterloo, Trang T. Nguyen, Melody Baddoo, Dorota Wyczechowska, Maria Morales, Yan Dong, Erik K. Flemington

School of Graduate Studies Faculty Publications

Virus genomes harbor compacted repertoires of genes and regulatory elements. Through long-read sequencing, we provide a comprehensive Epstein Barr virus (EBV) transcriptome analysis, identifying 1453 transcript isoforms and resolving the major isoform of all but one lytic reading frame. Further, we categorize each transcript according to their dependence on viral DNA replication. We show that the late gene viral preinitiation complex, vPIC also activates early promoters/genes, we identify active alternate promoters with distinct dependencies on viral DNA replication, we discover biphasic promoters with embedded features of both early and late promoters. Genetic and chromatin interaction studies identify an enhancer function …

Evaluation Of Pediatric Patients Diagnosed With Measles: A Retrospective Study In Istanbul, Zehra Yazi, Nahide Haykir Zehi̇r, Merve Akçay, Ufuk Yükselmiş, Ceren Çetin, Ayşe Karaaslan, Yasemin Akin

Journal of Pediatric Infectious Diseases

Objective: Measles, predominantly impacting the pediatric population, manifests symptoms encompassing fever, rash, rhinorrhea, cough, conjunctivitis, accompanied by infrequent yet plausible life-threatening complications.

Methods: This retrospective study conducted between January 2022 and July 2023 at a 1105-bed tertiary hospital in Istanbul, Türkiye, was focused on children diagnosed with measles and aged(PCR) were defined as definite measles cases.

Results: A total of 78 pediatric patients were diagnosed with measles, of whom 40 were evaluated as definite (51.3%) cases. Among the definite cases, 29 (72.5%) and 11 (27.5%) were girls and boys, respectively. Their median age was 78 (42–158) months. It was observed …

Overcoming Vaccine-Associated Enhanced Respiratory Disease In Swine Flu With Lipid Nanoparticle-Dna Technology, The Nguyen

School of Veterinary and Biomedical Sciences: Dissertations, Theses, and Student Research

The two primary challenges in developing vaccines against swine influenza A virus (IAV-S) are the continuous viral evolution and vaccine-associated enhanced respiratory disease (VAERD). Current vaccine strategies share a common limitation: the significant time required for licensing updated vaccines. Moreover, the strain selection for vaccine updates depends entirely on predictions, raising the risk that chosen strains may not match circulating viruses. Such mismatches not only reduce vaccine efficacy but also risk exacerbating disease severity through VAERD. Here, in this thesis, we developed and evaluated a novel DNA-based vaccine platform designed to address the need for rapid updates in response to …

A Retrospective Study Of Pulmonary Function Tests In Bronchiectasis: An Infectious Disease Of The Respiratory System, Vinod Mutkule, Mahesh Shinde, Vidya Bapmare, Sangramsingh Dixit, Atharva Sharma, Kshitij Sarwey, Yogeshwari Patil, Sanket Jethlia, Aayushi Dwivedi, Disha Pardeshi, Anmol Rai, Kunal Shah, Vidhi Kalwar

The University of Louisville Journal of Respiratory Infections

Introduction: Bronchiectasis, currently being recognized worldwide, is an abnormal dilatation of the bronchi and bronchioles brought on by recurrent cycles of inflammation and airway infection. Impaired pulmonary function has a predictive significance in bronchiectasis. When treating patients with suspected or confirmed respiratory diseases, pulmonary function tests (PFT) are useful examinations. Very few studies have been done on PFTs in bronchiectasis. The main aim of this study is to study PFTs in bronchiectasis.

Method: This is a retrospective observational study done on 50 patients over two years at the tertiary care center. The previous records of patients were collected from the …

Host Genetics Role In Viral Disease Susceptibility, Christian Willis Eaton

Dissertations and Doctoral Documents, University of Nebraska-Lincoln, 2023–

Viruses and their hosts exist in an evolutionary arms race, with evolutionary promotion of host genetic-based defense mechanisms and evolution of virus genetic-based mechanisms to overcome host defenses. Viruses are capable of much more rapid evolution and adaptation than their hosts, often leading to the use of host cellular mechanisms to promote viral infection and replication. In this study, we describe the generation of a detection assay for atypical porcine pestivirus (APPV), designed to target the viral 5’ UTR, a region of the viral genome which sees less mutations than the protein coding regions. This assay was generated to be …

Aerosolized Transmissible Diseases Guidance Document, J. David Miller, John P. (Jack) Springston Jr., Cheryl L. Marcham, J. David Krause, Ling-Ling Hung, Wane A. Baker

Publications

Prior to COVID-19, pandemic influenza viruses have emerged four times in the previous one hundred years. This includes “Spanish” influenza (H1N1) in 1918, “Asian” influenza (H2N2) in 1957, “Hong Kong” influenza (H3N2) in 1968, and H1N1 “swine” influenza in 2009 (Saunders-Hastings & Krewski, 2016; Taubenberger, 2005). In early May 2024, the first reported human case of avian flu (H5N1) that had also infected cows in the US appeared in the literature (Uyeki et al., 2024). In late August 2024, OSHA released a hazard alert providing information for dairy workers on avian influenza in dairy cattle, together with personal protective equipment …

Persistent Barriers To Implementation Of Long-Acting Injectable Antiretroviral Therapy, Jessica Hack, Adati Tarfa, Harlan Sayles, Nada Fadul

EMET Projects

No abstract provided.

From Pregnancy To Beyond: Renewed Emphasis On Comprehensive Hiv Prevention In South Africa., Chibuzor M. Babalola, Remco P.H. Peters, Christina A. Muzny, Dvora Joseph Davey, Christopher M. Taylor, Mandisa M. Mdingi, Freedom Mukomana, Lindsey De Vos, Andrew Medina-Marino, Jeffrey D. Klausner

School of Medicine Faculty Publications

No abstract provided.

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, …

Jarisch-Herxheimer Reaction After Benzathine Penicillin G Treatment In Adults With Early Syphilis: Secondary Analysis Of A Randomized Clinical Trial., Jodie A. Dionne, Chunming Zhu, Jorge Mejia-Galvis, Kimberly Workowski, Teresa A. Batteiger, Julia C. Dombrowski, Kenneth H. Mayer, Candice J. Mcneil, Arlene C. Seña, Stephanie Taylor, Harold C. Wiesenfeld, Matthew M. Hamill, Charlotte Perlowski, Edward W. Hook Iii

School of Medicine Faculty Publications

Key Points: Question: What proportion of patients with early syphilis have symptoms of the Jarisch-Herxheimer reaction (JHR) after treatment with benzathine penicillin G, and what are the associated characteristics? Findings: This prespecified secondary analysis of a multisite US randomized clinical trial found that, among 249 adults with early syphilis, JHR symptoms occurred after benzathine penicillin G treatment in 59 participants (23.7%). Onset of JHR was within 12 hours of treatment for 86.0% of participants, and JHR was associated with successful treatment response, secondary syphilis, and absence of HIV. Meaning: This study suggests that patients treated with benzathine penicillin G for …

Characteristics And Outcomes Of Adults Hospitalized With Respiratory Syncytial Virus, Brian S. Shaw, Cara Slaton, Ian P. Murphy, Michael Mcalister, Daniel Egan, Kwabena Ayesu

The University of Louisville Journal of Respiratory Infections

Background: Respiratory syncytial virus (RSV) is a negative sense single-stranded RNA virus (ssRNA) that primarily causes respiratory infections in both children and older adults. We examined clinical characteristics and outcomes of hospitalized adult patients who tested positive for RSV.

Methods: This was a multicenter, retrospective, descriptive study that examined adult patients admitted with a positive RSV test over two years across eight hospitals in Orlando, Florida.

Results: A total of 120 patients were included, of which 88 (73%) were 60 years old and older. Overall, patients with RSV infection were caucasian (62%) with a median age of 70 years and …

Dataset For Comparative Analysis Of Precision Metagenomics And Traditional Methods In Urinary Tract Infection Diagnostics, Rob E. Carpenter, Sadia Almas, Vaibhav Tamrakar, Rahul Sharma

Human Resource Development Faculty Publications and Presentations

This study presents a comprehensive dataset comparing three diagnostic methodologies—microbial culture, polymerase chain reaction (PCR), and precision metagenomics (precision metagenomics)—for the detection and classification of uropathogens in urine samples from patients with suspected urinary tract infections (UTIs). While microbial culture remains the gold standard for UTI diagnosis, it has limitations in sensitivity, particularly for fastidious or non-culturable microorganisms. PCR offers higher sensitivity but is restricted to pre-targeted organisms, limiting its diagnostic range. Precision Metagenomics, a target-agnostic sequencing method, provides a more inclusive approach by enabling the identification of a broad spectrum of pathogens, including bacteria, viruses, fungi, and parasites, without …

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 …

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 …

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 …

Forecasting Covid-19 Cases, Hospital Admissions, And Deaths Based On Wastewater Sars-Cov-2 Surveillance Using Gaussian Copula Time Series Marginal Regression Model, Hueiwang Anna Jeng, Norou Diawara, Cynthia Jackson, Rekha Singh, Kyle Curtis, Raul Gonzalez, David Jurgens, Sasanka Adikari

Epidemiology, Biostatistics, & Environmental Health Faculty Publications

Modeling efforts are needed to predict trends in COVID-19 cases and related health outcomes, aiding in the development of management strategies and adaptation measures. This study was conducted to assess whether the SARS-CoV-2 viral load in wastewater could serve as a predictor for forecasting COVID-19 cases, hospitalizations, and deaths using copula-based time series modeling. SARS-CoV-2 RNA load in wastewater in Chesapeake, VA, was measured using the RT-qPCR method. A Gaussian copula time series (CTS) marginal regression model, incorporating an autoregressive moving average model and Gaussian copula function, was used as a forecasting model. Wastewater SARS-CoV-2 viral loads were correlated with …

Interobserver Variability Regarding Adequacy Of Oropharyngeal Exposure For Transoral Robotic Surgery May Necessitate Staging Endoscopy: Evaluating Tors Exposure, Colleen Schinderle, Kevin J. Carlson, Reem Sharaf Alddin, Jeffery J. Houlton, Matthew J. Bak, Daniel W. Karakla, Jonathan R. Mark

Department of Otolaryngology (ENT) Faculty Publications

[First paragraph] Transoral robotic surgery (TORS) for the treatment of oropharyngeal cancer has become centered at tertiary referral centers. To avoid treatment delays or multiple anesthetics, the need for repeat operative endoscopy may be questioned when the diagnosis has been made at an outside institution. However, inadequate visualization of relevant anatomy can preclude TORS candidacy and may lead to procedure abortion or conversion to an open technique.²,³ To evaluate this dilemma, we explored the ability to assess oropharyngeal exposure for TORS candidacy via operative endoscopic photo-documentation.

Formulation Development Of Dual-Compartment Topical Inserts Combining Tenofovir Alafenamide And Elvitegravir For Flexible On-Demand Hiv Prevention, Vivek Agrahari, M. Melissa Peet, Neelima Chandra, Prakash Ramalingam, Pardeep K. Gupta, Sriramakamal Jonnalagadda, Onkar N. Singh, Timothy J. Mccormick, Gustavo F. Doncel, Meredith R. Clark

Department of Obstetrics & Gynecology Faculty Publications

Pre-exposure prophylaxis (PrEP) has emerged as a prominent approach for the prevention of HIV infections. While the latest advances have resulted in effective oral and injectable product options, there are still gaps in on-demand, event-driven, topical products for HIV prevention that are safe and effective. Here we describe the formulation development of a dual-compartment topical insert containing tenofovir alafenamide fumarate (TAF) and elvitegravir (EVG) that may be administered when needed, vaginally or rectally, pre- or post-coitus, for flexible HIV prophylaxis. Specifically, we describe the lab-scale formulation development, preclinical mucosal safety and pharmacokinetics (PK) testing in rabbits, long-term stability, and scale-up …

The Ptp4a3 Inhibitor Kvx-053 Reduces Severe Acute Respiratory Syndrome Coronavirus 2 (Sars-Cov-2) Virulence, Inflammation, And Development Of Acute Lung Injury In K18-Hace2 Mice, Ruben M. L. Colunga-Biancatelli, Pavel A. Solopov, Caitlin M. Woodson, Irving Coy Allen, Ivan Akhrymuk, Maryna Akhrymuk, Brittany N. Heath, Hannah M. Ivester, Tierney Day, Dan E. Austin, Kylene Kehn-Hall, John S. Lazo, Elizabeth R. Sharlow, John D. Catravas

Bioelectrics Publications

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has caused a global health crisis, marked by high transmissibility and virulence. Despite widespread vaccination efforts, effective treatments for COVID-19, particularly for severe cases leading to Acute Respiratory Distress Syndrome (ARDS), remain limited. This study investigates the efficacy of KVX-053, a protein tyrosine phosphatase type IVA (PTP4A3) small molecule inhibitor, in modulating SARS-CoV-2-induced inflammation and lung injury using in vitro cell models and in vivo K18-hACE2 transgenic mice. KVX-053 reduced in vitro pro-inflammatory cytokine expression, including TNFα, CXCL10, and CXCL11, without impacting viral replication or cell viability. K18-hACE2 mice treated with KVX-053 demonstrated …

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 …