Diseases Commons^™

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

Mathematics, Physics, and Computer Science Faculty Articles and Research

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

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 …

Ensemble-Based Mutational Profiling And Network Analysis Of The Sars-Cov-2 Spike Omicron Xbb Lineages For Interactions With The Ace2 Receptor And Antibodies: Cooperation Of Binding Hotspots In Mediating Epistatic Couplings Underlies Binding Mechanism And Immune Escape, Nishank Raisinghani, Mohammed Alshahrani, Grace Gupta, Gennady M. Verkhivker

Mathematics, Physics, and Computer Science Faculty Articles and Research

In this study, we performed a computational study of binding mechanisms for the SARS-CoV-2 spike Omicron XBB lineages with the host cell receptor ACE2 and a panel of diverse class one antibodies. The central objective of this investigation was to examine the molecular factors underlying epistatic couplings among convergent evolution hotspots that enable optimal balancing of ACE2 binding and antibody evasion for Omicron variants BA.1, BA2, BA.3, BA.4/BA.5, BQ.1.1, XBB.1, XBB.1.5, and XBB.1.5 + L455F/F456L. By combining evolutionary analysis, molecular dynamics simulations, and ensemble-based mutational scanning of spike protein residues in complexes with ACE2, we identified structural stability and binding …

Comparative Analysis Of Conformational Dynamics And Systematic Characterization Of Cryptic Pockets In The Sars-Cov-2 Omicron Ba.2, Ba.2.75 And Xbb.1 Spike Complexes With The Ace2 Host Receptor: Confluence Of Binding And Structural Plasticity In Mediating Networks Of Conserved Allosteric Sites, Mohammed Alshahrani, Grace Gupta, Sian Xiao, Peng Tao, Gennady M. Verkhivker

Mathematics, Physics, and Computer Science Faculty Articles and Research

In the current study, we explore coarse-grained simulations and atomistic molecular dynamics together with binding energetics scanning and cryptic pocket detection in a comparative examination of conformational landscapes and systematic characterization of allosteric binding sites in the SARS-CoV-2 Omicron BA.2, BA.2.75 and XBB.1 spike full-length trimer complexes with the host receptor ACE2. Microsecond simulations, Markov state models and mutational scanning of binding energies of the SARS-CoV-2 BA.2 and BA.2.75 receptor binding domain complexes revealed the increased thermodynamic stabilization of the BA.2.75 variant and significant dynamic differences between these Omicron variants. Molecular simulations of the SARS-CoV-2 Omicron spike full-length trimer complexes …

Exploring Conformational Landscapes And Cryptic Binding Pockets In Distinct Functional States Of The Sars-Cov-2 Omicron Ba.1 And Ba.2 Trimers: Mutation-Induced Modulation Of Protein Dynamics And Network-Guided Prediction Of Variant-Specific Allosteric Binding Sites, Gennady M. Verkhivker, Mohammed Alshahrani, Grace Gupta

Mathematics, Physics, and Computer Science Faculty Articles and Research

A significant body of experimental structures of SARS-CoV-2 spike trimers for the BA.1 and BA.2 variants revealed a considerable plasticity of the spike protein and the emergence of druggable binding pockets. Understanding the interplay of conformational dynamics changes induced by the Omicron variants and the identification of cryptic dynamic binding pockets in the S protein is of paramount importance as exploring broad-spectrum antiviral agents to combat the emerging variants is imperative. In the current study, we explore conformational landscapes and characterize the universe of binding pockets in multiple open and closed functional spike states of the BA.1 and BA.2 Omicron …

The Impact Of Vaccinations And Chronic Disease On Covid Death Rates, James L. Doti

Economics Faculty Articles and Research

This study presents a theoretical and empirical regression model to measure the efficacy of vaccinations in reducing COVID death rates across states over the 3/10/21 to 12/28/22 period. During that period, it was estimated that the availability of vaccinations resulted in a reduction of 427,000 COVID deaths in the nation. To arrive at that estimate, other covariants were held constant. In particular, it was found that chronic disease should be included as an explanatory variable to arrive at unbiased measures of the efficacy of vaccinations in reducing deaths. In addition, the percentage of people over the age of 65 was …

Metapopulation Dynamics Of Sars-Cov-2 Transmission In A Small-Scale Amazonian Society, Thomas Kraft, Edmond Seabright, Sarah Alami, Samuel M. Jenness, Paul L. Hooper, Bret Beheim, Helen Davis, Daniel K. Cummings, Daniel Eid Rodriguez, Maguin Gutierrez Cayuba, Emily J. Miner, Xavier De Lamballerie, Lucia Inchauste, Stéphane Priet, Benjamin Trumble, Jonathan Stieglitz, Hillard Kaplan, Michael Gurven

ESI Publications

The severity of infectious disease outbreaks is governed by patterns of human contact, which vary by geography, social organization, mobility, access to technology and healthcare, economic development, and culture. Whereas globalized societies and urban centers exhibit characteristics that can heighten vulnerability to pandemics, small-scale subsistence societies occupying remote, rural areas may be buffered. Accordingly, voluntary collective isolation has been proposed as one strategy to mitigate the impacts of COVID-19 and other pandemics on small-scale Indigenous populations with minimal access to healthcare infrastructure. To assess the vulnerability of such populations and the viability of interventions such as voluntary collective isolation, we …

Positive Changes In Safety Perception Among Blacks With Hiv And Comorbidities: Assessment Of Social Determinants Of Health During Covid‑19, Marc Fleming, Deidra Lee, Chukwuezugo Oranu, Jon C. Schommer, Jennifer M. Cocohoba, Jennifer Cooper, Crystal K. Hodge, Saharnaz Nedjat, Kathleen Borgmann

Pharmacy Faculty Articles and Research

Purpose

This study aimed to examine the impact of the COVID-19 lockdown on social determinants of health (SDOH) among Blacks with HIV and a comorbid diagnosis of hypertension or type 2 diabetes mellitus (T2DM).

Methods

This was a longitudinal survey study. The inclusion criteria were adults ≥ 18 years and the presence of hypertension and/or diabetes, along with a positive HIV diagnosis. This study enrolled patients in the HIV clinics and chain specialty pharmacies in the Dallas-Fort Worth (DFW) area. A survey of ten questions examining SDOH was conducted before, during, and after the lockdown. A proportional odds mixed effects …

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

Mathematics, Physics, and Computer Science Faculty Articles and Research

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

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

Mathematics, Physics, and Computer Science Faculty Articles and Research

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

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 …

The Effectiveness Of Pay-It-Forward In Addressing Hpv Vaccine Delay And Increasing Uptake Among 15–18-Year-Old Adolescent Girls Compared To User-Paid Vaccination: A Study Protocol For A Two-Arm Randomized Controlled Trial In China, Yifan Li, Chuanyu Qin, Shengyue Qiu, Yu He, Linchuan Pang, Xiaolan Xu, Vivian Wan-Cheong Yim, Shenglan Tang, Heng Du, Wenfeng Gong, Fan Yang, Joseph D. Tucker, Weiming Tang, Yun Wang, Leesa Lin, Mark Jit, Wei Song, Chunrong Li, Jennifer Smith, Jing Li, Dan Wu

Pharmacy Faculty Articles and Research

Background

Human papillomavirus (HPV) vaccination could prevent cervical and other HPV-associated cancers attributable to vaccine-associated HPV types. However, HPV vaccination coverage among women aged 9–18 years old is low in China. Common barriers include poor financial affordability, minimal public engagement, and low confidence in domestically produced HPV vaccines. Pay-it-forward offers an individual a free or subsidized service then an opportunity to voluntarily donate and/or create a postcard message to support future people. This study aims to assess the effectiveness of pay-it-forward as compared to standard-of-care self-paid vaccination to improve HPV vaccine uptake among adolescent girls aged 15–18 years, who are …

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, …

Effects Of Transcranial Direct Current Stimulation On Adults With Post-Acute Covid-19 Syndrome, Isaac Min, Aaron Schurger

Student Scholar Symposium Abstracts and Posters

Since its detection in December 2019, coronavirus disease 2019 (COVID-19), the viral disease caused by the SARS-CoV-2 novel coronavirus, has had prominent effects on human health and mortality. Studies in previous infections of SARS-CoV and MERS-CoV have found evidence of persistent symptoms in recovered patients, such as lethargy and shortness of breath. Similar residual symptoms have also been seen in recovered COVID-19 patients beyond four weeks of the initial onset of symptoms — collectively termed post-acute COVID-19 syndrome (PACS). These symptoms include deficits in working memory. Preliminary studies done in the United States and Europe have shown a significant portion …

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, …

Probing Mechanisms Of Binding And Allostery In The Sars-Cov-2 Spike Omicron Variant Complexes With The Host Receptor: Revealing Functional Roles Of The Binding Hotspots In Mediating Epistatic Effects And Communication With Allosteric Pockets, Gennady M. Verkhivker, Steve Agajanian, Ryan Kassab, Keerthi Krishnan

Mathematics, Physics, and Computer Science Faculty Articles and Research

In this study, we performed all-atom MD simulations of RBD–ACE2 complexes for BA.1, BA.1.1, BA.2, and BA.3 Omicron subvariants, conducted a systematic mutational scanning of the RBD–ACE2 binding interfaces and analysis of electrostatic effects. The binding free energy computations of the Omicron RBD–ACE2 complexes and comprehensive examination of the electrostatic interactions quantify the driving forces of binding and provide new insights into energetic mechanisms underlying evolutionary differences between Omicron variants. A systematic mutational scanning of the RBD residues determines the protein stability centers and binding energy hotpots in the Omicron RBD–ACE2 complexes. By employing the ensemble-based global network analysis, we …

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 …

Men’S Stories: An Account Of Translating Vaccine Decision Narratives From Young Men In The U.S. Into A Targeted Public Health Intervention, Michelle Miller-Day, Erin S. Craw, Diana Harris, Michael L. Hecht

Communication Faculty Articles and Research

Effective interventions to promote human papillomavirus (HPV) vaccination are needed for all young adults across the globe. Yet, most public health efforts focus on HPV-related risks for females. Unfortunately, HPV-related cancers in men are also a concern, as is the potential for men to spread HPV to their partners. The HPV vaccine is highly effective in reducing risks related to these cancers. Yet, vaccination rates among young males are low and their vaccination concerns are not well understood. This project conducted 15 in-depth qualitative interviews with U.S. males aged 18–22 to hear their vaccine decision stories. Themes of HPV vaccination …

The Impact Of Hpv Vaccine Narratives On Social Media: Testing Narrative Engagement Theory With A Diverse Sample Of Young Adults, Amy E. Leader, Michelle Miller-Day, Rikishi T. Rey, Preethi Selvan, Anne E. Pezalla, Michael L. Hecht

Communication Faculty Articles and Research

Rates of human papillomavirus (HPV) infection are highest in young adults, who can be vaccinated against HPV if they were not vaccinated as adolescents. Since young adults increasingly access health information on social media, we tested the impact of a social media campaign with narrative-based health information on intentions related to HPV vaccination. We also aimed to understand which ads resonated most with young adults and led to higher survey completion rates. We created social media posts featuring videos promoting HPV vaccination. We launched a sponsored ad campaign on Facebook to reach young women, ages 18–26, across the country. Participants …

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 …

Integrating Conformational Dynamics And Perturbation-Based Network Modeling For Mutational Profiling Of Binding And Allostery In The Sars-Cov-2 Spike Variant Complexes With Antibodies: Balancing Local And Global Determinants Of Mutational Escape Mechanisms, Gennady M. Verkhivker, Steve Agajanian, Ryan Kassab, Keerthi Krishnan

Mathematics, Physics, and Computer Science Faculty Articles and Research

n this study, we combined all-atom MD simulations, the ensemble-based mutational scanning of protein stability and binding, and perturbation-based network profiling of allosteric interactions in the SARS-CoV-2 spike complexes with a panel of cross-reactive and ultra-potent single antibodies (B1-182.1 and A23-58.1) as well as antibody combinations (A19-61.1/B1-182.1 and A19-46.1/B1-182.1). Using this approach, we quantify the local and global effects of mutations in the complexes, identify protein stability centers, characterize binding energy hotspots, and predict the allosteric control points of long-range interactions and communications. Conformational dynamics and distance fluctuation analysis revealed the antibody-specific signatures of protein stability and flexibility of the …

Biophysical Insight Into The Sars-Cov2 Spike–Ace2 Interaction And Its Modulation By Hepcidin Through A Multifaceted Computational Approach, Hamid Hadi-Alijanvand, Luisa Di Paola, Guang Hu, David M. Leitner, Gennady M. Verkhivker, Peixin Sun, Humanath Poudel, Alessandro Giuliani

Mathematics, Physics, and Computer Science Faculty Articles and Research

At the center of the SARS-CoV2 infection, the spike protein and its interaction with the human receptor ACE2 play a central role in the molecular machinery of SARS-CoV2 infection of human cells. Vaccine therapies are a valuable barrier to the worst effects of the virus and to its diffusion, but the need of purposed drugs is emerging as a core target of the fight against COVID19. In this respect, the repurposing of drugs has already led to discovery of drugs thought to reduce the effects of the cytokine storm, but still a drug targeting the spike protein, in the infection …

The Impact Of The Covid-19 Pandemic On Care Delivery And Quality Of Life In Lung Cancer Surgery, Dede K. Teteh, Jovani Barajas, Betty Ferrell, Ziaoke Zhou, Loretta Erhunmwunsee, Dan J. Raz, Jae Y. Kim, Virginia Sun

Health Sciences and Kinesiology Faculty Articles

Background

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (COVID-19) pandemic and associated restrictions have altered the delivery of surgical care. The purpose of this study was to explore the impact of COVID-19 on care delivery and quality of life (QOL) from the perspectives of lung cancer surgery patients, family caregivers (FCGs), and thoracic surgery teams.

Methods

Patients/FCGs enrolled in a randomized trial of a self-management intervention for lung cancer surgery preparation/recovery were invited to participate in this qualitative study. Patients/FCGs data were collected separately 1-month postdischarge. Interviews were also conducted with thoracic surgery team members. Content analysis approaches were …

Computer Simulations And Network-Based Profiling Of Binding And Allosteric Interactions Of Sars-Cov-2 Spike Variant Complexes And The Host Receptor: Dissecting The Mechanistic Effects Of The Delta And Omicron Mutations, Gennady M. Verkhivker, Steve Agajanian, Ryan Kassab, Keerthi Krishnan

Mathematics, Physics, and Computer Science Faculty Articles and Research

In this study, we combine all-atom MD simulations and comprehensive mutational scanning of S-RBD complexes with the angiotensin-converting enzyme 2 (ACE2) host receptor in the native form as well as the S-RBD Delta and Omicron variants to (a) examine the differences in the dynamic signatures of the S-RBD complexes and (b) identify the critical binding hotspots and sensitivity of the mutational positions. We also examined the differences in allosteric interactions and communications in the S-RBD complexes for the Delta and Omicron variants. Through the perturbation-based scanning of the allosteric propensities of the SARS-CoV-2 S-RBD residues and dynamics-based network centrality and …

Allosteric Determinants Of The Sars-Cov-2 Spike Protein Binding With Nanobodies: Examining Mechanisms Of Mutational Escape And Sensitivity Of The Omicron Variant, Gennady M. Verkhivker

Mathematics, Physics, and Computer Science Faculty Articles and Research

Structural and biochemical studies have recently revealed a range of rationally engineered nanobodies with efficient neutralizing capacity against the SARS-CoV-2 virus and resilience against mutational escape. In this study, we performed a comprehensive computational analysis of the SARS-CoV-2 spike trimer complexes with single nanobodies Nb6, VHH E, and complex with VHH E/VHH V nanobody combination. We combined coarse-grained and all-atom molecular simulations and collective dynamics analysis with binding free energy scanning, perturbation-response scanning, and network centrality analysis to examine mechanisms of nanobody-induced allosteric modulation and cooperativity in the SARS-CoV-2 spike trimer complexes with these nanobodies. By quantifying energetic and allosteric …

Conformational Flexibility And Local Frustration In The Functional States Of The Sars-Cov-2 Spike B.1.1.7 And B.1.351 Variants: Mutation-Induced Allosteric Modulation Mechanism Of Functional Dynamics And Protein Stability, Gennady M. Verkhivker

Mathematics, Physics, and Computer Science Faculty Articles and Research

Structural and functional studies of the SARS-CoV-2 spike proteins have recently determined distinct functional states of the B.1.1.7 and B.1.351 spike variants, providing a molecular framework for understanding the mechanisms that link the effect of mutations with the enhanced virus infectivity and transmissibility. A detailed dynamic and energetic analysis of these variants was undertaken in the present work to quantify the effects of different mutations on functional conformational changes and stability of the SARS-CoV-2 spike protein. We employed the efficient and accurate coarse-grained (CG) simulations of multiple functional states of the D614G mutant, B.1.1.7 and B.1.351 spike variants to characterize …

Development Of A Bamlanivimab Infusion Process In The Emergency Department For Outpatient Covid-19 Patients, Danny Pham, Sandy Wong, Christina T. Nguyen, Stephen C. Lee, Kimberly J. Won

Pharmacy Faculty Articles and Research

The coronavirus disease 2019 (COVID-19) pandemic has prompted the creation of new therapies to help fight against the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Bamlanivimab is a SARS-CoV-2 monoclonal antibody that is administered as an intravenous infusion to ambulatory patients with mild or moderate COVID-19, but a concern that arose was deciding the optimal location for patients to receive the medication. This report describes the development and implementation of a bamlanivimab infusion center in the emergency department of three hospitals in Orange County, California, shortly after bamlanivimab received emergency use authorization. As a result, a total of 601 …

Maintaining Physical Activity During Covid-19: The Influence Of Psychosocial Variables In Individuals With Back Pain, Heidi Stabbert

Student Scholar Symposium Abstracts and Posters

Stressor events, such as COVID-19, may trigger adaptive or maladaptive pain management strategies among individuals with persistent low back pain (LBP). Individuals with lower fear avoidance, depression and anxiety, and greater positive affect and quality of life may better maintain positive pain management strategies during stressor events. This study investigated psychosocial characteristics of individuals with LBP who demonstrated adaptive pain management strategies during COVID-19, indicated by maintenance of physical activity (PA). Individuals with persistent LBP (age 22.4 (3.4) years, n=25) from an existing longitudinal cohort participated. Participants completed a baseline survey prior to COVID-19 quantifying demographics, pain characteristics, the Physical …

Atomistic Simulations And In Silico Mutational Profiling Of Protein Stability And Binding In The Sars-Cov-2 Spike Protein Complexes With Nanobodies: Molecular Determinants Of Mutational Escape Mechanisms, Gennady M. Verkhivker, Steve Agajanian, Deniz Yasar Oztas, Grace Gupta

Mathematics, Physics, and Computer Science Faculty Articles and Research

Structure-functional studies have recently revealed a spectrum of diverse high-affinity nanobodies with efficient neutralizing capacity against SARS-CoV-2 virus and resilience against mutational escape. In this study, we combine atomistic simulations with the ensemble-based mutational profiling of binding for the SARS-CoV-2 S-RBD complexes with a wide range of nanobodies to identify dynamic and binding affinity fingerprints and characterize the energetic determinants of nanobody-escaping mutations. Using an in silico mutational profiling approach for probing the protein stability and binding, we examine dynamics and energetics of the SARS-CoV-2 complexes with single nanobodies Nb6 and Nb20, VHH E, a pair combination VHH E + …

Suppression Of Dc-Sign And Gh Reveals Complex, Subset-Specific Mechanisms For Kshv Entry In Primary B Lymphocytes, Nancy Palmerin, Farizeh Aalam, Romina Nabiee, Murali Muniraju, Javier Gordon Ogembo, Jennifer Totonchy

Pharmacy Faculty Articles and Research

Kaposi sarcoma-associated herpesvirus (KSHV) is the causative agent of multiple cancers in immunocompromised patients including two lymphoproliferative disorders associated with KSHV infection of B lymphocytes. Despite many years of research into the pathogenesis of KSHV associated diseases, basic questions related to KSHV molecular virology remain unresolved. One such unresolved question is the cellular receptors and viral glycoproteins needed for KSHV entry into primary B lymphocytes. In this study, we assess the contributions of KSHV glycoprotein H (gH) and the cellular receptor DC-SIGN to KSHV infection in tonsil-derived B lymphocytes. Our results show that (1) neither KSHV-gH nor DC-SIGN are essential …