Virus Diseases Commons^™

Sirt1 And Ifi16 Cooperatively Regulate Hbv Replication Via Epigenetic Modulation And Innate Immune Activation, Zahra Zahid Piracha, Umar Saeed, Neelam Abid, Syed Shahan Gilani, Hafiz Ahmad Bilal Akhtar Chughtai, Areesha Wasti, Muhammad Waseem, Dilber Uzun Ozsahin, Andromeda M. Nauli, Surya M. Nauli

Pharmacy Faculty Articles and Research

Background

Hepatitis B virus (HBV) establishes persistent infection through the formation of a covalently closed circular DNA (cccDNA) minichromosome, which enables immune evasion and sustained viral replication. While SIRT1, IFI16, and STING are known to modulate antiviral pathways, their cooperative role in regulating HBV transcription and host immunity remains poorly defined.

Methods

We investigated the functional interplay between SIRT1, IFI16, and STING using confocal microscopy, chromatin immunoprecipitation (ChIP), gene silencing, and quantitative PCR in HBV-replicating cell models. Interactions with HBV cccDNA and effects on viral transcription and interferon-stimulated gene (ISG) expression were analyzed. Northern blotting and RT-qPCR were used to …

Expert Recommendations To Strengthen Chikungunya Outbreak Surveillance And Reporting For Traveler Health Protection, Daniel C. Payne, Karoun H. Bagamian, Jeffery Goad, Nathan D. Grubaugh, Michael A. Johansson, Moritz U. G. Kraemer, Eyal Leshem, Francesca F. Norman, Alfonso J. Rodríguez-Morales, Henrik Salje, Stephen Thomas, Scott C. Weaver, Lindsey A. Laytner, Rebecca Sturgis, Suzanne K. Scheele, Davidson H. Hamer

Pharmacy Faculty Articles and Research

Chikungunya, a debilitating mosquito-borne disease caused by chikungunya virus, has surged dramatically in the past two decades. Chikungunya outbreaks can intensify rapidly, with infections posing a significant endemic health burden in tropical/subtropical areas and for travelers. Health professionals require timely and accurate outbreak information to adequately protect travelers and assess chikungunya risk. However, detection is often insufficient in the areas most susceptible to outbreaks, leading to diagnostic and reporting delays. Consequently, travelers are often unaware of increased chikungunya infection risk at their destination. We assessed chikungunya surveillance and reporting resources, and we developed expert recommendations for traveler health protection. Because …

Early And Sustained Improvements In Sense Of Smell With Tezepelumab Treatment In Patients With Chronic Rhinosinusitis With Nasal Polyps (Waypoint), Joaquim Mullol, Joseph K. Han, Tanya M. Laidlaw, Claire Hopkins, Anju T. Peters, Oliver Pfaar, Martin Desrosiers, Stella E. Lee, Andrew P. Lane, Claudia Chen, Yun Chon, Sandhia S. Ponnarambil, Andrews Foster, Andrew W. Lindsley, Christopher S. Ambrose

Department of Otolaryngology (ENT) Faculty Publications

Background

Loss of smell is a principal symptom of chronic rhinosinusitis with nasal polyps (CRSwNP), affecting health-related quality of life and posing a safety hazard.

Methods

WAYPOINT (NCT04851964), a phase 3, multicenter trial in adults with uncontrolled CRSwNP, randomized patients 1:1 to receive tezepelumab 210 mg or placebo subcutaneously every 4 weeks for 52 weeks. Changes from baseline in biweekly mean Nasal Polyposis Symptom Diary (NPSD) loss of smell item, University of Pennsylvania Smell Identification Test (UPSIT), and 22-item Sino-Nasal Outcome Test (SNOT-22) loss of smell/taste item scores, as well as anosmia (UPSIT score ≤18) prevalence, were assessed over 52 …

Identifying Barriers For Community Pharmacies As Vaccines For Children (Vfc) Providers In Rural Alabama: Opportunities For Solutions, Myra Bajwa

Honors Theses

Significant Human papillomavirus (HPV) vaccination disparities exist between rural and urban areas in the US. A primary contributor is low access to preventive care in rural areas. Among the most promising strategies to overcome this is increasing access through offering HPV vaccination in non-traditional, convenient health settings such as pharmacies. In rural areas, community pharmacies are trusted, convenient pillars of the community. In Alabama, community pharmacies are eligible for enrollment in the Vaccines for Children (VFC) Program, a federally-funded program that provides free vaccines to children and adolescents under 18 years old who are uninsured, underinsured, American Indian, or Alaska …

Evolutionary Pathways Of Drug Resistance To Long-Acting Prep In Initial Hiv Infection, Yeona Kang, Katharine Gurski, Yanping Ma

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

Kshv Vil6 Inhibits Functional B Cell Maturation During De Novo Infection, Wajd Zakir, Jessica M. Osborn, Jennifer Totonchy

Pharmacy Faculty Articles and Research

Despite causative links to lymphoproliferative disorders, little is known about early events governing KSHV infection in B lymphocytes. IL-6 signaling plays a critical role in KSHV-mediated disease, with human IL-6 (hIL6) levels correlating with viral load and disease progression. This dynamic is even more complex due to the coexistence of hIL6 and KSHV-encoded viral IL-6 (vIL6) in these diseases. We hypothesize that hIL6 and vIL6 play critical, separable and collective roles in the early stages of KSHV infection in B cells. In this study, we use our ex vivo model of KSHV infection in human tonsil lymphocytes to investigate the …

The Design, Construction, And Testing Of Mrna Vaccine Against Equine Herpes Virus, Bhawana Devkota

LSU Master's Theses

Equine Herpesvirus-1 (EHV 1) is a worldwide significant pathogen that causes respiratory illness, abortion, and neurological disorders in equine. Current vaccines, including live attenuated, inactivated, and subunit platforms, do not prevent viral latency, mucosal shedding, or cross-strain immunity, requiring alternative approaches. To address these gaps, this project explores the design, synthesis, and in vitro testing of an mRNA vaccine targeting immunogenic EHV 1 glycoprotein (gB, gC, gD, gG, and gM). Epitopes were computationally predicted using the Immune Epitope Database (IEDB), codon-optimized for Bos taurus, and cloned into pUCIDT vectors using SP6/T7 promoters. In vitro transcription (IVT) used nucleotide modifications …

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 …

Investigating The Extent To Which Diet-Induced Obesity Alters Gene Expression In Hematopoietic Stem And Progenitor Cells Following Influenza Immunization In Mice, Chaitanya Lahari Chowdary Pathipati

Theses, Dissertations and Capstones

Vaccines are a vital tool in preventing diseases, but their effectiveness varies depending on factors like diet and body weight. Obese individuals often experience reduced vaccine protection, as seen with influenza vaccines, where they have twice the risk of getting the flu compared to healthy-weight individuals after vaccination. This study aims to understand why obesity weakens vaccine effectiveness, focusing on the role of blood-forming stem cells in the bone marrow, known as hematopoietic stem and progenitor cells (HSPCs). These cells are crucial for producing immune cells that defend the body against infections. Previous research has shown that diet-induced obesity alters …

The Role Of Peptides In Combatting Hiv Infection: Applications And Insights, Naiera M. Helmy, Keykavous Parang

Pharmacy Faculty Articles and Research

Peptide-based inhibitors represent a promising approach for the treatment of HIV-1, offering a range of potential advantages, including specificity, low toxicity, and the ability to target various stages of the viral lifecycle. This review outlines the current state of research on peptide-based anti-HIV therapies, highlighting key advancements and identifying future research directions. Over the past few years, there has been significant progress in developing synthetic peptide-based drugs that target various stages of the viral life cycle, including entry and replication. These approaches aim to create effective anti-HIV therapies. Additionally, peptides have proven valuable in the development of anti-HIV vaccines. In …

A Tale Of Two Bills: Lessons Learned In Expanding Pharmacist-Led Hiv Pre-Exposure And Post-Exposure Prophylaxis, Jennifer M. Cocohoba, Jerika Lam, Maria Lopez, Betty J. Dong

Pharmacy Faculty Articles and Research

"In December 2023, JACCP published a content analysis of state legislative bills focused on expanding pharmacist scope of practice to provide human immunodeficiency virus (HIV) pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP).¹ All states permit pharmacists to prescribe under a collaborative practice agreement with approximately half of the states granting HIV PrEP and post-exposure prophylaxis (PEP) authority to prescribe either via legislation, standing orders, or statewide protocols.^2-4 New York was the first state to expand pharmacists' specific authority for HIV prevention in 2017; however, California was the first state to pass legislation with Senate Bill 159 …

At A Crossroads: The Crucial Role Of Pharmacists In Healthcare Teams To End The Hiv Epidemic, Jerika Lam, Jennifer M. Cocohoba

Pharmacy Faculty Articles and Research

"Therapeutic advances in treatment and prevention have slowed the human immunodeficiency virus (HIV) epidemic, yet the virus and complications related to it still claim an alarming 630,000 lives globally every year.^1,2 The United States’ goals for the Ending the HIV Epidemic (EHE) initiative include reducing new infections by 90% by the year 2030 and advancing health equity through key treatment and prevention initiatives.³ Multiple agencies, professions, and patient groups are working diligently to achieve the EHE goals. Pharmacists have long recognized that our profession is a key resource in ending the HIV epidemic. We demonstrate this in the …

A Third Generation Long-Acting Dimeric Dolutegravir Prodrug Nanoformulation, Bhoomika Suresh Gowda

Theses & Dissertations

Dolutegravir (DTG) is an integrase strand transfer inhibitor (INSTI) widely used as a part of first-line combination antiretroviral therapy. DTG has a high barrier to resistance However, one therapeutic challenge centers on its life-long daily use. Sub-optimal adherence to daily oral pills underscore the need for long-acting formulations. To these ends, our research activities have focused on the development and translation of ultra-long-acting ART. Monomeric ester prodrugs provided initial success in extending the apparent half-life of DTG and other INSTIs. One is the DTG prodrug formulation called NM2DTG. NM2DTG’s significantly extended the parent drug’s apparent half-life [Nature Communications, 3226 (2022)]. …

Development Of A Novel Drug Delivery Platform To Treat Hiv-Associated Neurocognitive Disorder, Lina Zhou

Alternative Theses and Dissertations (AETDs)

Despite the significant reduction in HIV prevalence and improvement in life expectancy achieved through the availability of widespread antiretroviral therapy (ART), there remains no definitive cure for HIV. Further, HIV infects the brain as early as eight days after initial peripheral infection leading to neuroHIV and subsequently neuronal damage and cognitive impairment. HIV can enter the brain through several mechanisms, including the migration of infected immune cells (Trojan Horse Mechanism), direct infection of endothelial cells, and cytokine-mediated disruption of the blood-brain barrier (BBB). Consequently, HIV-associated neurocognitive disorder (HAND) remains a significant challenge in the ART era, with an estimated prevalence …

Impact Of A Pharmacist-Led Hcv Treatment Program At A Federally Qualified Health Center, Jerika T. Lam, Sharon Xavioer

Pharmacy Faculty Articles and Research

Pharmacists are key players who can help to eliminate the hepatitis C virus (HCV) epidemic in the United States. This pilot retrospective study evaluated the impact of a pharmacist-led HCV treatment program in a federally qualified health center (FQHC) primary care clinic setting. The primary outcome was to assess sustained virologic response (SVR) rates 12 weeks after patients were initiated and completed their oral direct acting antiviral (DAA) treatment regimens. Methods: This pilot retrospective study included historical analyses of patients who received DAA treatment in the pharmacist-led HCV treatment program in a FQHC clinic between 1 January 2019 and 31 …

Translational Pathways For Ultra Long-Acting Medicines For Chronic Disease: From Hiv To Substance Use Disorders, Suyash Sanjay Deodhar

Theses & Dissertations

Human immunodeficiency virus (HIV) and opioid use disorder (OUD) are among the top global public health challenges, with a significant overlap in the number of cases and higher mortality risks compared to the general population. Treatment and recreational opioid use lead to addictive disorders. Both conditions require repeated dosing of therapy where adherence to a strict lifelong regimen remains a major challenge. Notably, people living with HIV/AIDS (PLWHA) and struggling with opioid use disorders (OUD) show suboptimal adherence to antiretroviral drugs (ARVs). Also, the risk of transmitting HIV and other blood-borne infections through the sharing of needles and other injection …

Development Of Long-Acting Antiviral And Antimicrobial Prodrug Nanoformulations, Srijanee Das

Theses & Dissertations

Over the past decade, the global burden of infectious diseases has increased substantively, underscoring the need for more effective treatment strategies. However, the discovery and development of new drugs with desirable safety, pharmacokinetics, and efficacy is a time consuming and costly process with great uncertainty around success rate. As an alternative to new drug development, prodrugs and novel drug delivery systems have increasingly been explored. Both serve to overcome the drug development challenges. Such drug formulations that permit extended dosing intervals of potent native drugs serve multiple purposes by promoting patient adherence to in improving treatment outcomes. This is especially …

Broad-Spectrum Activity Of Membranolytic Cationic Macrocyclic Peptides Against Multi-Drug Resistant Bacteria And Fungi, Sandeep Lohan, Anastasia G. Konshina, Rakesh K. Tiwari, Roman G. Efremov, Innokentiy Maslennikov, Keykavous Parang

Pharmacy Faculty Articles and Research

The emergence of multidrug-resistant (MDR) strains causes severe problems in the treatment of microbial infections owing to limited treatment options. Antimicrobial peptides (AMPs) are drawing considerable attention as promising antibiotic alternative candidates to combat MDR bacterial and fungal infections. Herein, we present a series of small amphiphilic membrane-active cyclic peptides composed, in part, of various nongenetically encoded hydrophilic and hydrophobic amino acids. Notably, lead cyclic peptides 3b and 4b showed broad-spectrum activity against drug-resistant Gram-positive (MIC = 1.5–6.2 µg/mL) and Gram-negative (MIC = 12.5–25 µg/mL) bacteria, and fungi (MIC = 3.1–12.5 µg/mL). Furthermore, lead peptides displayed substantial antibiofilm action comparable …

Various Synthetic Pathways Towards Efavirenz And Its Analogs; The Replacement Of The Side Chain, Elizabeth S. Bautista

Selected Honors Theses

Cyclopropyl acetylene (CA) is a key intermediate in the synthesis of the human immunodeficiency virus (HIV) reverse transcriptase inhibitor, Efavirenz (EFV), an antiviral drug used to treat HIV. CA is an expensive raw material, difficult to obtain, and employed in the preparation of medications to combat acquired immunodeficiency syndrome (AIDS). It was found that the structure could be synthesized by the utilization of PCl5; however, this resulted in unwanted ring opening products. To address this issue, a one pot synthesis was developed using Ph3PCl2 as a mild chlorinating agent. In addition, a new analog has been proposed substituting the cyclopropyl …

Debunking Old Evolution Theories, Proposing New One (Near Neutral Balanced Selection Theory/Nnbst) Using Sars Cov 2 Genomic Data, Chun Wu

College of Science & Mathematics Departmental Research

The COVID 19 pandemic has caused 672 million infections and 6 million deaths understanding the molecular evolution of this virus is critical to ending this pandemic • The SARS CoV 2 genome exhibits a time independent, constant genomic substitution rate ( despite increasing vaccinations and infected human cases (Figure 1 A) • Out of the three main evolutionary theories S electionist Theory/ST, Kimura’s Neutral Theory/KNT, Ohta’s Nearly Neutral Theory/ONNT), the SARS CoV 2 GSR seemingly follows KNT but this does not explain the critical intervention by vaccines and therapeutic drugs on the evolution of this virus I n this study …

Virtual And In Vitro Screening Of Natural Products Identifies Indole And Benzene Derivatives As Inhibitors Of Sars-Cov-2 Main Protease (MPro), Dony Ang, Riley Kendall, Hagop S. Atamian

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

The rapid spread of the coronavirus disease 2019 (COVID-19) resulted in serious health, social, and economic consequences. While the development of effective vaccines substantially reduced the severity of symptoms and the associated deaths, we still urgently need effective drugs to further reduce the number of casualties associated with SARS-CoV-2 infections. Machine learning methods both improved and sped up all the different stages of the drug discovery processes by performing complex analyses with enormous datasets. Natural products (NPs) have been used for treating diseases and infections for thousands of years and represent a valuable resource for drug discovery when combined with …

Il-21 Signaling Promotes The Establishment Of Kshv Infection In Human Tonsil Lymphocytes By Increasing Differentiation And Targeting Of Plasma Cells, Nedaa Alomari, Jennifer Totonchy

Pharmacy Faculty Articles and Research

Introduction: Factors influencing Kaposi’s sarcoma-associated herpesvirus (KSHV) transmission and the early stages of KSHV infection in the human immune system remain poorly characterized. KSHV is known to extensively manipulate the host immune system and the cytokine milieu, and cytokines are known to influence the progression of KSHV-associated diseases. Our previous work identified the early targeting of plasma cells for KSHV infection. In this study, we examine whether IL-21, a cytokine known to profoundly influence plasma cell fate, influences the early stages of KSHV infection in B lymphocytes.

Methods: Using our unique model of ex vivo KSHV infection in tonsil lymphocytes, …

Host-Level Susceptibility And Irf1 Expression Influence The Ability Of Ifn-Γ To Inhibit Kshv Infection In B Lymphocytes, Nedaa Alomari, Jennifer Totonchy

Pharmacy Faculty Articles and Research

Kaposi’s sarcoma-associated herpesvirus (KSHV) is associated with vascular endothelial cell tumor, Kaposi’s sarcoma (KS) and lymphoproliferative disorder, multicentric Castleman’s disease (MCD), primary effusion lymphoma (PEL) and KSHV inflammatory cytokine syndrome (KICS). Dysregulation of proinflammatory cytokines is found in most KSHV associated diseases. However, little is known about the role of host microenvironment in the regulation of KSHV establishment in B cells. In the present study, we demonstrated that IFN-γ has a strong inhibitory effect on KSHV infection but only in a subset of tonsil-derived lymphocyte samples that are intrinsically more susceptible to infection, contain higher proportions of naïve B cells, …

Novel Drugs Approved In 2021-2022, Michael Do, Bona Shin, Elaina Lioudis, Emaleigh Munn

Transformative Medicine

This article provides an abbreviated overview of the newly Federal Drug Administration (FDA)approved novel drugs of 2021-2022 with their respective approved indication(s). The FDA serves as the governing body that regularly evaluates and approves medications that will eventually be introduced to the market for routine use. These medications include both drugs that are the same or related to previously approved products (e.g., Extended indications of priorly approved medications) and novel drugs. By definition, a novel drug is an innovative product which serves to improve quality care in patient populations with unmet or advanced medical needs to overall advance patient care …

Nanotherapeutics And Hiv: Four Decades Of Infection Canvass The Quest For Drug Development Using Nanomedical Technologies, Bhupender S. Chhikara, Nirpendra Singh, Poonam, Parveen Bazard, Rajender S. Varma, Keykavous Parang

Pharmacy Faculty Articles and Research

We have seen four decades of human struggle to cure or eradicate HIV infection since the first clinical detection of HIV infection. Various developed drugs such as nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors, integrase inhibitors, microbicides, and others have known restrictions, such as side effects and resistance development when used alone, and hidden reservoir of the virus, which have opened the gates for the involvement of nanomedicine associated systems, particularly for latent sites of HIV infection. The nanotechnological vehicles, such as liposomes, dendrimers, metal nanoparticles, polymeric nanocapsules/particles, surfactants, and targeted vehicles have become part …

Synthesis And Evaluation Of Anti-Hiv Activity Of Mono- And Di-Substituted Phosphonamidate Conjugates Of Tenofovir, Aaminat Qureshi, Louise A. Ouattara, Naglaa Salem El-Sayed, Amita Verma, Gustavo F. Doncel, Muhammad Iqbal Choudhary, Hina Siddiqui, Keykavous Parang

Pharmacy Faculty Articles and Research

The activity of nucleoside and nucleotide analogs as antiviral agents requires phosphorylation by endogenous enzymes. Phosphate-substituted analogs have low bioavailability due to the presence of ionizable negatively-charged groups. To circumvent these limitations, several prodrug approaches have been proposed. Herein, we hypothesized that the conjugation or combination of the lipophilic amide bond with nucleotide-based tenofovir (TFV) (1) could improve the anti-HIV activity. During the current study, the hydroxyl group of phosphonates in TFV was conjugated with the amino group of L-alanine, L-leucine, L-valine, and glycine amino acids and other long fatty ester hydrocarbon chains to synthesize 43 derivatives. Several …

Ameliorative Effects Of Minor Cannabinoids Over Hiv-1 Tat-Mediated Visceral Pain, Charlie Worth

Honors Theses

As the total number of people living with HIV continues to rise across the world, an effective HIV treatment is still sought after. While modern-day advanced therapies exist for mitigating much of the negative effects of HIV, the virus remains evasive and problematic in the central nervous system. Thus, even with treatment, many people living with HIV continue to suffer from a plethora of symptoms. However, a large proportion of HIV-positive patients claim to feel a reduction in those persevering symptoms after cannabis usage. This anecdotal evidence has sparked interest in the efficacy of cannabis constituents for HIV therapy. This …

Interrogating Race And Place-Based Inequities In Hiv And Covid-19, Rohan Khazanchi

EMET Projects

Over the last four years, I have developed a research focus examining the intersections of race, place, and health. My M.D. Honors Thesis reflects a snapshot of these efforts. In this collection of brief research reports, I leverage area-based measures to investigate structural inequities in three contexts: the HIV epidemic in our hyperlocal community, the early stages of the COVID-19 pandemic, and clinical trials for novel COVID-19 therapeutics. I apply novel social epidemiologic tools to measure and explore disparate outcomes. And, in reflecting upon my findings, I discuss concrete implications for clinicians, researchers, and policymakers alike.

Chapter 1: Neighborhood-Level Deprivation …

A Quantitative Analysis Of The Efficacy Of Various Essential Oils Against The Sars Cov-2 Virus, Elizabeth Wagstaff, Chandrelyn Kraczek, Jack Brandon Lopez

Annual Research Symposium

A poster presentation and abstract for the Roseman Symposium. The project focuses on testing 3 essential oil blends and two disinfectants containing an essential oil blend against SARS CoV-2 in response to the COVID-19 pandemic. The project procedure involves plaque assays, disinfection, and neutralization techniques.

“Hiccups” With Covid-19 Management, Yong W. Lee, Jacob Psomiadis, Sarah Akbani, Marvin Lopez-Medal, Aisha Miller

Advances in Clinical Medical Research and Healthcare Delivery

Hiccups, medically referred as singultus, is a condition that results from involuntary contraction of the diaphragm and intercostal muscles. Singultus is usually a self-limiting condition which typically lasts less than 48 hours but in rare cases, can persist greater than 48 hours. This is a case of a 48 year-old male who was prescribed dexamethasone for COVID-19 but developed intractable singultus for two weeks. Patient was unable to tolerate diet due to intractable singultus leading to vomiting. He underwent various non-pharmacological maneuvers and pharmacotherapy without resolution. Dexamethasone- induced hiccups have been reported as an under recognized side effect of dexamethasone. …