Virus Diseases Commons^™

Comparative Antiviral Activity Of Remdesivir And Anti-Hiv Nucleoside Analogs Against Human Coronavirus 229e (Hcov-229e), Keykavous Parang, Naglaa Salem El-Sayed, Assad J. Kazeminy, Rakesh Tiwari

Pharmacy Faculty Articles and Research

Remdesivir is a nucleotide prodrug that is currently undergoing extensive clinical trials for the treatment of COVID-19. The prodrug is metabolized to its active triphosphate form and interferes with the action of RNA-dependent RNA polymerase of SARS-COV-2. Herein, we report the antiviral activity of remdesivir against human coronavirus 229E (HCoV-229E) compared to known anti-HIV agents. These agents included tenofovir (TFV), 4′-ethynyl-2-fluoro-2′-deoxyadenosine (EFdA), alovudine (FLT), lamivudine (3TC), and emtricitabine (FTC), known as nucleoside reverse-transcriptase inhibitors (NRTIs), and a number of 5′-O-fatty acylated anti-HIV nucleoside conjugates. The anti-HIV nucleosides interfere with HIV RNA-dependent DNA polymerase and/or act as chain terminators. …

Vaccines In Current Culture: The Hpv Vaccine Controversy, Alyssa Johnston

Senior Honors Theses

The use of vaccinations has drastically decreased mortality and morbidity rates related to infectious disease and has become an intrinsic part of modern health care. However, the fear of risks related to vaccines has been partially responsible for the decisions of many parents to delay or avoid vaccinating their children. The human papilloma virus (HPV) vaccine specifically is one of the most controversial vaccines in current culture due to reports of new onset or exacerbation of autoimmune diseases, infertility, and even death following its administration. This review synthesizes information regarding the relevance and safety of the HPV vaccine, as well …

A Real-World Analysis Of Patient Characteristics And Predictors Of Hospitalization Among Us Medicare Beneficiaries With Respiratory Syncytial Virus Infection, Veronique Wyffels, Furaha Kariburyo, Sandra Gavart, Roman Fleischhackl, Huseyin Yuce

Publications and Research

Introduction: Little has been published on respiratory syncytial virus (RSV) among Medicare patients at high risk (HR) of RSV complications due to age or comorbidity. Methods: Adult patients (at least 18 years of age) with at least 1 diagnostic code for RSV were identified using the 5% US Medicare database from 2011 through 2015. Patients were required to have continuous health plan enrollment for 180 days pre- and 180 days post-RSV diagnosis (baseline and follow-up periods, respectively). HR was defined as diagnosis of chronic lung disease, congestive heart failure, or weakened immune system for 180 days during the base-line period. …

Tobacco/Hiv-1-Induced Myeloid Cell-Derived Extracellular Vesicles In Hiv-1 Pathogenesis, Sanjana Haque

Theses and Dissertations (ETD)

Introduction. Smoking, which is highly prevalent in people living with HIV/AIDS, has been shown to exacerbate HIV-1 replication, in part via cytochrome P450 (CYP)-induced oxidative stress. CYP enzymes metabolize cigarette smoke condensate (CSC), causing oxidative stress and cytotoxicity. Our previous studies have demonstrated that CSC and specific CSC constituents, benzo(a)pyrene and nicotine, potentially induce CYPs, resulting in higher oxidative stress and subsequent exacerbation of HIV-1 replication in monocytes and macrophages. However, the exact mechanism behind tobacco-induced, oxidative stress-mediated enhancement of HIV-1 replication is still poorly understood. Extracellular vesicles (EVs) have recently gained attention for their unique nature as intercellular messengers …

Updates On Human Immunodeficiency Virus (Hiv), Jose Ojeda

All Publications

No abstract provided.

Updates On Human Immunodeficiency Virus (Hiv), Eduardo Martinez Sanchez

All Publications

No abstract provided.

Vaccine Hesitancy: Experimentalism As Regulatory Opportunity, Ana Santos Rutschman, Timothy L. Wiemken

All Faculty Scholarship

This symposium on patient innovation has prompted us to explore problems related to departures from official vaccination schedules. At a time in which vaccine confidence has been plummeting across the world, we argue that a more granular understanding—and ultimately a more finely tuned regulatory framework—is needed to reflect the current behavioral heterogeneity among indicated patients who choose to forego or delay administration of recommended vaccines. In particular, we focus on a phenomenon we term “vaccine staggering:” a departure from vaccination schedules in the form of delays in receiving one or more vaccines, which is motivated by the desire to boost …

Synthesis And Characterization Of Long Acting Darunavir Prodrugs, Mary Banoub

Theses & Dissertations

Patient adherence is critical for ART success to ensure adequate viral suppression, therefore, long-acting antiretrovirals are soon replacing current daily regimens. In recent years, two drugs were successfully transformed into long-acting injectables; CAB LA and RPV LA. These long-acting nanoformulations made it possible to abandon the daily pill burden, instead approximately a bimonthly injection of both drugs is enough to suppress and maintain viral load suppression. Our laboratory has been instrumental in transforming FDA-approved and experimental-HIV medications into long-acting slow effective release drugs, also known as LASER ART. LASER ART consists of slow drug metabolism and high permeability and retention …

Theranostics For Antiretroviral Biodistribution And Pharmacokinetics, Brendan M. Ottemann

Theses & Dissertations

RATIONALE: Our laboratories birthed the field of human immunodeficiency virus (HIV) theranostics. The new field allows simultaneous detection (diagnostics) and treatment (therapeutic) for the identification, treatment and inevitable elimination of virus in cell and tissue compartments. By employing theranostics, antiretroviral drugs (ARVs) can be tracked in lymph nodes, gut, spleen and liver. Cellular viral reservoirs including CD4+ T cell populations and mononuclear phagocytes (MP; monocytes, macrophages, microglia and dendritic cells) along with subcellular endosomal structures can now be targeted for drug delivery bringing therapeutics to areas where virus replicates. The overarching idea rests in improving precision targeted ARV delivery. …

Zika Virus Induced Neurological Disorders And Impacts On Public Health, Alexandra Herman, Martha Zimmerman, Olivia Vanscoy, Olivia Henton, Lindsey Peters

Pharmacy and Wellness Review

Zika virus is a public health emergency of international concern. Zika virus (ZIKV) is a mosquito-borne pathogen that is carried by the Aedes genus. Zika is spread through direct bite and nonvector transmission. Most individuals infected with Zika will be asymptomatic, but some may present nonspecific viral symptoms. A rising number of neurological disorders in newborns whose mothers were infected with ZIKV during pregnancy have been reported due to recent outbreaks. Neurological disorders affect both the central and peripheral nervous systems and can result from bacterial, viral, fungal or parasitic infections of the nervous system or from the immune response …

Zika Virus: Infectious Process And Public Health Response, Morgan Homan, Julia Dickman, Jenna Deininger, Austin Hopkins, Olivia Henton, Steven N. Leonard

Pharmacy and Wellness Review

The Zika virus has become a growing concern as a global pandemic. Since being identified in Uganda in 1947, the virus has spread around the world, recently emerging in South America with a great impact on Brazil. As of 2016, Zika has made its appearance in the United States and is now actively being transmitted in Florida. The virus is a mosquito-vectored flavivirus primarily transmitted by the Aedes mosquito which infects a human through biting. Transmission through sexual intercourse is also possible as well as transmission from a pregnant woman to her fetus. This latter form of transmission presents the …

Laboratory Mutations Of H5n1 Confer Efficient Transmission In Animal Models And Generate International Debate Regarding Publication Of Dual Use Research, Morgan A. Belling, Kelly Dye, Joshua Ilenin, Jamie Amero, Andrew M. Roecker

Pharmacy and Wellness Review

H5N1, a subtype of influenza A virus that originated in Hong Kong in 1997 and has since spread across Asia and Africa, features a reported case fatality rate of nearly 60 percent in humans. Although naturally-occurring H5N1 has not developed the ability to be efficiently transmitted from human to human, two independent research teams have recently mutated strains of the virus, resulting in facile transmission among laboratory ferrets, which are considered the most accurate models for humans in viral studies. As a consequence of the security and public health risks of such information, the U.S. National Science Advisory Board for …

A Community-Based Survey To Assess Knowledge, Attitudes, Beliefs And Practices Regarding Herpes Zoster In An Urban Setting, Nour A. Baalbaki, Joseph P. Fava, Melanie Ng, Ezinwanne Okorafor, Asad Nawaz, Wesley Chiu, Abdulbaset Salim, Raymond Cha, Paul E. Kilgore

Department of Pharmacy Practice

Introduction: In the USA, nearly one in three people will experience herpes zoster (HZ) in their lifetime. Underserved communities may be at even higher risk due to several factors, including access to healthcare, education, and co-morbid conditions. The purpose of this study was to investigate current knowledge, attitudes, beliefs and practices (KABP) relative to HZ and HZ vaccines in a large urban city.

Methods: A cross-sectional KABP survey was conducted via in-person interview among 381 participants aged ≥ 50 years in Detroit, MI, USA, from June to August 2018. Survey results were stratified into two groups [< 60 and ≥ 60 years of age (YO)] for comparison.

Results: Of the …

Synthesis And Characterization Of Long-Acting Rilpivirine Prodrugs, James R. Hilaire

Theses & Dissertations

Antiretroviral therapy (ART) requires lifelong daily dosing to suppress viral replication, restore or maintain immune function and improve quality of life. As an alternative, long-acting (LA) antiretrovirals (ARVs) aim to deliver therapeutic drug concentrations over an extended period, ultimately requiring monthly or even more extended dosing intervals. Specifically, the success of recent clinical trials examining LA cabotegravir and rilpivirine (CAB and RPV LA) highlight the advent of these novel HIV-1 therapeutics. Further optimization of LA dosage forms are required and rests upon improving dosing frequency, injection volumes and tissue distribution to viral compartments. To this end, we report the synthesis …

A Multivalent Kaposi Sarcoma-Associated Herpesvirus-Like Particle Vaccine Capable Of Eliciting High Titers Of Neutralizing Antibodies In Immunized Rabbits, David H. Mulama, Lorraine Z. Mustvunguma, Jennifer Totonchy, Peng Ye, Joslyn Foley, Gabriela M. Escalante, Esther Rodriguez, Ramina Nabiee, Murali Muniraju, Felix Wussow, Anne K. Barasa, Javier Gordon Ogembo

Pharmacy Faculty Articles and Research

Kaposi sarcoma-associated herpesvirus (KSHV) is an emerging pathogen and the causative agent of multiple cancers in immunocompromised patients. To date, there is no licensed prophylactic KSHV vaccine. In this study, we generated a novel subunit vaccine that incorporates four key KSHV envelope glycoproteins required for viral entry in diverse cell types (gpK8.1, gB, and gH/gL) into a single multivalent KSHV-like particle (KSHV-LP). Purified KSHV-LPs were similar in size, shape, and morphology to KSHV virions. Vaccination of rabbits with adjuvanted KSHV-LPs generated strong glycoprotein-specific antibody responses, and purified immunoglobulins from KSHV-LP-immunized rabbits neutralized KSHV infection in epithelial, endothelial, fibroblast, and B …

Shingrix Revaccination And Vaccination In Vulnerable Populations, Laressa Bethishou, Luma Munjy, John Andraos

Pharmacy Faculty Articles and Research

"Herpes zoster, also known as shingles, is a painful cutaneous eruption that develops following the reactivation of the varicella zoster virus (VZV), the same virus that causes chickenpox.¹ About 1 in 3 people in the United States will develop shingles, with an estimated 1 million cases occurring annually. Anyone with a history of chickenpox is at risk for shingles, but the risk increases with age and in patients who are immunocompromised.²"

Src Family Kinase Inhibitors Block Translation Of Alphavirus Subgenomic Mrnas, Rebecca Broeckel, Sanjay Sarkar, Nicholas A. May, Jennifer Totonchy, Craig N. Kreklywich, Patricia Smith, Lee Graves, Victor R. Defilippis, Mark T. Heise, Thomas E. Morrison, Nathaniel Moorman, Daniel N. Streblow

Pharmacy Faculty Articles and Research

Alphaviruses are arthropod-transmitted RNA viruses that can cause arthralgia, myalgia, and encephalitis in humans. Since the role of cellular kinases in alphavirus replication is unknown, we profiled kinetic changes in host kinase abundance and phosphorylation following chikungunya virus (CHIKV) infection of fibroblasts. Based upon the results of this study, we treated CHIKV-infected cells with kinase inhibitors targeting the Src family kinase (SFK)–phosphatidylinositol 3-kinase (PI3K)–AKT–mTORC signaling pathways. Treatment of cells with SFK inhibitors blocked the replication of CHIKV as well as multiple other alphaviruses, including Mayaro virus, O’nyong-nyong virus, Ross River virus, and Venezuelan equine encephalitis virus. Dissecting the effect of …

Hiv Integrase Inhibitor Pharmacogenetics And Clinical Outcomes: An Exploratory Association Study, Derek E. Murrell

Electronic Theses and Dissertations

As HIV is now primarily a chronic condition, treatment is given life-long with changes as necessitated by alterations in tolerability and efficacy. Thus, personalized medicine may be useful in the prevention of unnecessary drug exposure and avoidable side effects. Three of the four currently available HIV integrase strand transfer inhibitors (INSTIs), raltegravir, elvitegravir, and dolutegravir, are widely utilized antiretrovirals in the USA and exhibit variations in outcomes among subjects. To interrogate differences among subjects receiving these drugs, we investigated the association of several single nucleotide polymorphisms (SNPs) with drug exposure, clinical outcomes, and subject-reported adverse events. HIV+ adults (≥18 years …

Limiting Antibiotic Use In Acute Sinusitis: Partly A Matter Of Vocabulary?, Dennis J. Baumgardner

Journal of Patient-Centered Research and Reviews

In his issue introduction, the editor-in-chief of Journal of Patient-Centered Research and Reviews comments on an included article that describes the successful use of an electronic medical record best practice alert to reduce the rate of antibiotic prescription for acute sinusitis. Various methods previously tried to improve antibiotic stewardship in this illness are briefly reviewed. Borrowing on the model of acute bronchitis, it is suggested that a change in conveyed diagnostic vocabulary to “sinus cold” when describing acute sinusitis may help limit antibiotics for this predominantly viral infection.

Kshv Induces Immunoglobulin Rearrangements In Mature B Lymphocytes, Jennifer Totonchy, Jessica M. Osborn, Amy Chadburn, Ramina Nabiee, Lissenya Argueta, Geoffrey Mikita, Ethel Cesarman

Pharmacy Faculty Articles and Research

Kaposi sarcoma herpesvirus (KSHV/HHV-8) is a B cell tropic human pathogen, which is present in vivo in monotypic immunoglobulin λ (Igλ) light chain but polyclonal B cells. In the current study, we use cell sorting to infect specific B cell lineages from human tonsil specimens in order to examine the immunophenotypic alterations associated with KSHV infection. We describe IL-6 dependent maturation of naïve B lymphocytes in response to KSHV infection and determine that the Igλ monotypic bias of KSHV infection in vivo is due to viral induction of BCR revision. Infection of immunoglobulin κ (Igκ) naïve B cells induces expression …

Paclitaxel Enhances Oncolytic Potential Of Herpes Simplex Virus Type-1 In Cancer Cells, Misagh Naderi

LSU Master's Theses

Taxanes are spindle poisons that bind to and stabilize microtubules resulting in mitotic arrest. Herpes simplex Typ-1 (HSV-1) virions utilize the microtubular network for intracellular transport during both virus entry and virus egress from infected cells. It has been reported previously that taxanes may synergize with oncolytic herpes simplex viruses in the treatment of experimental prostate and breast tumors in mice. Other reports have indicated that taxanes may inhibit viral replication in infected cells. In this study the previously characterized Oncolytic Herpes Simplex Virus type 1 (OSVP), which was constructed in Kousoulas lab was used in conjugation with paclitaxel (taxol) …

Pneumonia Vaccines: Current Recommendations And Advocacy Opportunities, Laressa Bethishou

Pharmacy Faculty Articles and Research

"Despite the demonstrated efficacy of these vaccines, only 66.9% of adults over age 65 years have ever received a pneumonia vaccine. Given the consequences of acquiring pneumonia, there is both a need and an opportunity to improve vaccination rates. The pharmacist can play a valuable role in identifying high-risk patients, providing education on benefits and risks, and advocating for pneumonia vaccination when indicated."

Reducing Medication Errors In Pneumonia Patients During Transitions Of Care, Laressa Bethishou, Noah Fang, Lisa Shieh

Pharmacy Faculty Articles and Research

Purpose: At Stanford Health Care, as part of a hospital-wide initiative to reduce pneumonia readmission rates, an interdisciplinary collaborative effort was created between physicians and transitions of care (ToC) pharmacists to optimize discharge planning and medication management for pneumonia patients. The purpose of this study was to describe the impact of the ToC pharmacist in identifying and reducing medication errors on discharge for pneumonia patients.

Methodology: Retrospective chart review was conducted on patients discharged with a pneumonia diagnosis between December 2015 to Feb 2016. Patients were stratified based on whether they received ToC pharmacist medication review vs. standard …

Finding Human Proteins That Bind To A Lassa Virus Protein, Maria Alejandra Pardo Ruge, Veronica J. Heintz, Douglas J. Lacount

The Summer Undergraduate Research Fellowship (SURF) Symposium

Viral hemorrhagic fevers are severe illnesses caused by many different viruses. Lassa Virus is one of these important pathogens in Western Africa, causing hemorrhagic fever and eventually death without early medical treatment. There is no vaccine and there is little information on host-pathogen interactions. Therefore, the interaction between viral proteins and host targets is useful to understand Lassa virus’s lifecycle and pathology, and to develop ways to prevent infection. In this project, we study the nucleoprotein of Lassa virus (NP), which has been reported to have anti-interferon (IFN) activity through elimination of double stranded RNA (dsRNA). These features could be …

Synthesis And Evaluation Of Antimicrobial Activity Of [R4w4k]-Levofloxacin And [R4w4k]-Levofloxacin-Q Conjugates, Neda Riahifard, Kathy Tavakoli, Jason Yamaki, Keykavous Parang, Rakesh Tiwari

Pharmacy Faculty Articles and Research

The development of a new class of antibiotics to fight bacterial resistance is a time-consuming effort associated with high-cost and commercial risks. Thus, modification, conjugation or combination of existing antibiotics to enhance their efficacy is a suitable strategy. We have previously reported that the amphiphilic cyclic peptide [R4W4] had antibacterial activity with a minimum inhibitory concentration (MIC) of 2.97 g/mL against Methicillin-resistant Staphylococcus aureus (MRSA). Herein, we hypothesized that conjugation or combination of the amphiphilic cyclic peptide [R4W4] with levofloxacin or levofloxacin-Q could improve the antibacterial activity of levofloxacin and levofloxacin-Q. Fmoc/tBu solid-phase chemistry was employed to synthesize conjugates of …

Human Papillomavirus (Hpv): Current Status & Controversies, Ada Jalice

All Publications

No abstract provided.

Long-Acting Antiretroviral Nanoformulation Development And Subcellular Trafficking, Dongwei Guo

Theses & Dissertations

The introduction of nanoformulated antiretroviral therapeutic regimens is a promising alternative to standard once a day oral treatment of HIV infection. Our lab has pioneered this effort and was successful in harnessing mononuclear phagocytes (monocytes, dendritic cells and macrophages) as nanoformulated drug carriers. The approach was developed as Trojan horses for drug transport, delivery and distribution to sites of viral replication in order to facilitate microbial elimination in HIV sanctuaries. However, the remaining challenges for current antiretroviral nanoformulations include to formulate a broad range of hydrophilic short-acting drugs, and to elucidate the mechanism of sequestered nanoparticles in macrophages at the …

Stabilization Of Gp120 Outer Domain For Hiv-1-1 Vaccine Immunogen Design, Duoyi Hu

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

The sole envelope glycoprotein spike on the surface of Human Immunodeficiency Virus (HIV-1) is composed of two subunits: gp120 and gp41. The gp120 consists of three domains: the inner domain, outer domain and bridging sheet, to which the viral primary receptor CD4 binds and induces a conformational change in gp120 to expose the co-receptor binding site. Previous studies have found that the outer domain of gp120 is relatively more stable than the inner domain and bridging sheet. When superimposed, the co-crystal structures of CD4-gp120 complex and VRC01-gp120 complex revealed that the CD4-binding site (CD4-BS) antibody VRC01 actually mainly bound to …

A Community Hospital Antimicrobial Stewardship Program’S Assessment Of Prolonged Infusion Piperacillin-Tazobactam For Pseudomonas Aeruginosa Pneumonia, Lee Nguyen, Paul Gavaza, Amy Y. Kang, An Nguyen, Liem Hoang, Nguyen Ta

Pharmacy Faculty Articles and Research

Background: The study aim was to determine and compare the length of hospitalization, mortality, clinical stability, and time to clinical stability of a standard infusion (SI) and prolonged infusion (PI) piperacillin-tazobactam (TZP) in Pseudomonas aeruginosa ( PA) pneumonia patients.

Methods: This retrospective study evaluated length of hospitalization, mortality, clinical stability, and time to clinical stability with either SI-TZP or PI-TZP therapy in hospitalized patients diagnosed with PA pneumonia between January 01, 2008 and June 30, 2014. Patients were included in the study if they received ≥2 days of TZP, were diagnosed with PA pneumonia, and had TZP therapy …

Improving The Renal Profile Of A Hiv Drug Combination Through Prodrug Alteration, Derek E. Murrell, Sam Harirforoosh

Pharmacy Faculty Articles and Research

"Human immunodeficiency virus (HIV) continues to alter the lives of countless individuals, who once infected, live on a continuum between viral suppression and acquired immunodeficiency syndrome. The former being achieved via the use of various antiretrovirals beginning with the release of zidovudine over a quarter-century ago; whereas the latter may result from treatment failure or lack of treatment such as in the absence of diagnosis or the inaccessibility of medication. As no cure is yet available, regimens must be continued lifelong. Thus, contemporary treatment is given as a combination of agents from various antiretroviral drug classes in an effort to …