Immune System Diseases Commons^™

Uncovering Novel Mechanism Of Immune Modulation Of Invariant Natural Killer T Cells By Liposomal Α-Galactosylceramide, Alexandra S. Flegle

Dissertations and Theses (Open Access)

Invariant Natural Killer T cells (iNK-T cells) are a powerful regulatory immune cell that can recruit both innate and adaptive immune cells. Unlike conventional T cells (CD4⁺ and CD8α⁺), they recognize glycolipid antigens via the MHC-class-I like molecule, CD1d. A synthetically derived glycolipid from the marine sponge, Agelas mauritianus, alpha-Galactosylceramide (α-GalCer) potently activates iNK-T cells. Within a few hours after activation, iNK-T cells produce high quantities of T_H1 and T_H2 type cytokines, thus shape subsequent adaptive immunity towards inflammation (T_H1) or immune-suppression (T_H2). Structural modification of α-GalCer’s phytosphingosine …

Bladder Mucosal Cystitis Cystica Lesions Are Tertiary Lymphoid Tissues That Correlate With Recurrent Urinary Tract Infection Frequency In Postmenopausal Women, Marianne M Ligon, Brooke Liang, Stacy M Lenger, Priyanka Parameswaran, Siobhan Sutcliffe, Jerry L Lowder, Indira U Mysorekar

Faculty, Staff and Students Publications

PURPOSE: We identify correlates and clinical outcomes of cystitis cystica, a poorly understood chronic inflammatory bladder change, in women with recurrent urinary tract infections.

MATERIALS AND METHODS: A retrospective, observational cohort of women with recurrent urinary tract infections who underwent cystoscopy (n=138) from 2015 to 2018 were identified using electronic medical records. Cystitis cystica status was abstracted from cystoscopy reports and correlations were identified by logistic regression. Urinary tract infection-free survival time associated with cystitis cystica was evaluated by Cox proportional hazards regression. Exact logistic regression was used to identify factors associated with changes to cystitis cystica lesions on repeat …

Contribution Of Adaptive Immunity To Human Copd And Experimental Models Of Emphysema, Farrah Kheradmand, Yun Zhang, David B Corry

Faculty, Staff and Students Publications

The pathophysiology of chronic obstructive pulmonary disease (COPD) and the undisputed role of innate immune cells in this condition have dominated the field in the basic research arena for many years. Recently, however, compelling data suggesting that adaptive immune cells may also contribute to the progressive nature of lung destruction associated with COPD in smokers have gained considerable attention. The histopathological changes in the lungs of smokers can be limited to the large or small airways, but alveolar loss leading to emphysema, which occurs in some individuals, remains its most significant and irreversible outcome. Critically, however, the question of why …

Role Of Biomarkers (Sflt-1/Plgf) In Cases Of Covid-19 For Distinguishing Preeclampsia And Guiding Clinical Management, Guilherme M Nobrega, Jose P Guida, Juliana M Novaes, Larissa M Solda, Luciana Pietro, Adriana G Luz, Giuliane J Lajos, Carolina C Ribeiro-Do-Valle, Renato T Souza, Jose G Cecatti, Indira U Mysorekar, Tabata Z Dias, Maria Laura Costa

Faculty, Staff and Students Publications

OBJECTIVES: To analyze soluble fms-like tyrosine kinase 1 (sFlt-1) and placental growth factors (PlGF) concentrations and their ratio in pregnant and postpartum women with suspected COVID-19, and further investigate conditions associated with an increased ratio (sFlt-1/PlGF > 38), including preeclampsia (PE) and severe acute respiratory syndrome (SARS).

STUDY DESIGN: The present study is a secondary analysis of a prospective cohort. Blood samples were collected at time of COVID-19 investigation and the serum measurements of sFlt-1 and PlGF were performed. Clinical background, SARS-CoV-2 infection characteristics, maternal and perinatal outcomes were further analyzed.

MAIN OUTCOME MEASURES: Serum measurements of sFlt-1 and PlGF; obstetrics …

The Immunomodulating Effects Of Morphine Dependence And Withdrawal In A Rat Model, Mark Stoll

Annual Research Symposium

Would you like to know what happens to the immune system during opioid drug withdrawal?

Infiltrating Cd8+ T Cells Exacerbate Alzheimer’S Disease Pathology In A 3d Human Neuroimmune Axis Model, Jefin Jose, Devam Purohit

VCU's Medical Journal Club: The Work of Future Health Professionals

In this study, Jorfi et al. employed a neuroimmune axis model containing neurons, astrocytes, and microglia to examine the role of immune cells in Alzheimer's disease. Jorfi et al. found that T cells selectively infiltrated the BRAIN compartment of the neuroimmune axis model as compared to B cells and monocytes. Jorfi et al. further found that CD8+ T cells demonstrated heightened cytotoxicity in the Alzheimer's disease brain, illuminating the role of immune cells in neurodegeneration. Upon further examination, the CXCR3-CXCL10 signaling pathway was found to have an important role in inflammation.

A Genome-Wide In Vivo Crispr Screen Identifies Essential Regulators Of T Cell Migration To The Cns In A Multiple Sclerosis Model, Jefin Jose

VCU's Medical Journal Club: The Work of Future Health Professionals

Kendirli et al. (2023) used a CRISPR screen to determine the proteins involved in T cell migration into the CNS in multiple sclerosis. Overall, eighteen facilitators and five brakes to T cell infiltration into the CNS were identified. Kendirli et al. specifically identified ITGA4, FERMT3, and HSP90B1 to make up the adhesion module, CXCR3, GNAI2, and TBX21 to make up the chemotaxis module, and GRK2 and S1PR2 to make up the egress module. This study demonstrated the ability of a CRISPR screen to identify elements in a disease process and thus identify targets for future multiple sclerosis therapies.

Vitamin D Enhanced Vitamin D Receptor (Vdr) Inhibition Of Nlrp3 Inflammasome Activation Can Attenuate The Development Of Autoimmune Thyroiditis, Alexzon Mandac

Capstone Showcase

Autoimmune Thyroiditis (AIT) is a prevalent autoimmune disease affecting approximately 2% of the population. Characterized by the gradual loss of thyroid function through an autoimmune attack on the thyroid gland, the disease manifests symptoms that negatively affect one’s quality of life. The mechanisms behind the disease’s pathophysiology are not fully understood; however, researchers are examining the involvement of the NLRP3 inflammasome in the disease. This thesis will address the question of whether Vitamin D can act as an inhibitor of the NLRP3 inflammasome and attenuate the progression of AIT in mouse model. Current investigations explore the effects of NLRP3 inhibition …

Covid-19 And Pregnancy: Clinical Outcomes; Mechanisms, And Vaccine Efficacy, Deepak Kumar, Sonam Verma, Indira U Mysorekar

Faculty, Staff and Students Publications

As the COVID-19 pandemic continues into its third year, emerging data indicates increased risks associated with SARS-CoV-2 infection during pregnancy, including pre-eclampsia, intrauterine growth restriction, preterm birth, stillbirth, and risk of developmental defects in neonates. Here, we review clinical reports to date that address different COVID-19 pregnancy complications. We also document placental pathologies induced by SARS-CoV-2 infection, entry mechanisms in placental cells, and immune responses at the maternal-fetal interface. Since new variants of SARS-CoV-2 are emerging with characteristics of higher transmissibility and more effective immune escape strategies, we also briefly highlight the genomic and proteomic features of SARS-CoV-2 investigated to …

Alveolar Macrophages In Lung Cancer: Opportunities Challenges, Cheng-Yen Chang, Dominique Armstrong, David B Corry, Farrah Kheradmand

Faculty, Staff and Students Publications

Alveolar macrophages (AMs) are critical components of the innate defense mechanism in the lung. Nestled tightly within the alveoli, AMs, derived from the yolk-sac or bone marrow, can phagocytose foreign particles, defend the host against pathogens, recycle surfactant, and promptly respond to inhaled noxious stimuli. The behavior of AMs is tightly dependent on the environmental cues whereby infection, chronic inflammation, and associated metabolic changes can repolarize their effector functions in the lungs. Several factors within the tumor microenvironment can re-educate AMs, resulting in tumor growth, and reducing immune checkpoint inhibitors (ICIs) efficacy in patients treated for non-small cell lung cancer …

Effects Of Aging On Urinary Tract Epithelial Homeostasis And Immunity, Marianne M Ligon, Chetanchandra S Joshi, Bisiayo E Fashemi, Arnold M Salazar, Indira U Mysorekar

Faculty, Staff and Students Publications

A global increase in older individuals creates an increasing demand to understand numerous healthcare challenges related to aging. This population is subject to changes in tissue physiology and the immune response network. Older individuals are particularly susceptible to infectious diseases, with one of the most common being urinary tract infections (UTIs). Postmenopausal and older women have the highest risk of recurrent UTIs (rUTIs); however, why rUTIs become more frequent after menopause and during old age is incompletely understood. This increased susceptibility and severity among older individuals may involve functional changes to the immune system with age. Aging also has substantial …

Engaging Patients In Antimicrobial Stewardship: Co-Designed Educational Tool To Improve Periprocedural Care Through De-Implementation Of Guideline-Discordant Antimicrobial Use, Hawra Al Lawati, Marlena Shin, Rebecca Lamkin, Tyler Thompson, Isabella Epshtein, Hillary Mull, Dipandita Basnet Thapa, Dimitri Drekonja, Maria C Rodriguez-Barradas, Teena Huan Xu, Howard Gold, A Rani Elwy, Judy Strymish, Westyn Branch-Elliman

Faculty, Staff and Students Publications

Effective de-implementation models often include replacement of an ineffective practice with an alternative. We co-developed patient education materials as a replacement strategy for inappropriate post-procedural antibiotics in cardiac device procedures. Lessons learned and developed materials may be used to promote infection prevention in other periprocedural settings.

The Mechanisms Of Mitochondrial Dysfunction In T Cell Aging During Chronic Viral Infection, Madison B. Schank

Electronic Theses and Dissertations

Human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infections induce a myriad of disturbances to CD4 T cell functions, including mitochondrial compromise, excessive inflammation, increased telomeric DNA damage and attrition, cellular exhaustion and senescence, and accelerated aging. In this dissertation, the mechanisms underlying metabolic failure, accelerated aging, and cellular dysfunctions were evaluated in CD4 T cells from healthy subjects (HS) treated with a telomere-targeting drug (KML001) or HCV-infected individuals or people living with HIV (PLHIV) compared to HS. We observed that KML001-induced telomere injury resulted in mitochondrial swelling and decreased mitochondrial membrane potential, cellular respiration, mitochondrial DNA (mtDNA) copy …

Investigating The Pi3k/Akt/Atm Pathway, Telomeric Dna Damage, T Cell Death, And Crispr/Cas9-Mediated Gene Editing During Acute And Chronic Hiv Infection, Sushant Khanal

Electronic Theses and Dissertations

Human Immunodeficiency Virus (HIV) infection initiates major metabolic and cell- survival complications. Anti-retroviral therapy (ART) is the current approach to suppress active HIV replication to a level of undetected viral load, but it is not a curative approach. Newer and sophisticated gene editing technologies could indeed be a potent antiviral therapy to achieve a clinical sterilization/cure of HIV infection. Chronic HIV patients, even under a successful ART regimen, exhibit a low-grade inflammation, immune senescence, premature aging, telomeric DNA attrition, T cell apoptosis, and cellular homeostasis. In this dissertation, we investigated CD4 T cell homeostasis, degree of T cell apoptosis, an …

Expert Clinical Management Of Severe Immune-Related Adverse Events: Results From A Multicenter Survey On Hot Topics For Management, Mar Riveiro-Barciela, Maria Jose Soler, Ana Barreira-Diaz, Sheila Bermejo, Sebastian Bruera, Maria E Suarez-Almazor

Faculty, Staff and Students Publications

There are differences in recommendations for the management of immune-related adverse events (irAEs) associated with immune checkpoint inhibitors (ICIs). To assess the real-world management of irAEs, three surveys regarding ICI-induced hepatitis (IIH), renal irAEs, and myositis were developed and sent to experts in each area. Fifty-six surveys were completed (17 IIH, 20 renal irAEs, and 19 myositis). All experts agreed on performing imaging in every suspected case of severe IIH. Sixty-five percent agreed on performing a liver biopsy in patients not responding to corticosteroids. The most common indication for corticosteroid use (59%) was for severe IIH not improving after discontinuation …

Stem Cell Transplantation For Systemic Sclerosis, Sebastian Bruera, Harish Sidanmat, Donald A Molony, Maureen D Mayes, Maria E Suarez-Almazor, Kate Krause, Maria Angeles Lopez-Olivo

Faculty, Staff and Students Publications

BACKGROUND: Systemic sclerosis (SSc) is a chronic autoimmune disease characterized by systemic inflammation, fibrosis, vascular injury, reduced quality of life, and limited treatment options. Autologous hematopoietic stem cell transplantation (HSCT) has emerged as a potential intervention for severe SSc refractory to conventional treatment.

OBJECTIVES: To assess the benefits and harms of autologous hematopoietic stem cell transplantation for the treatment of systemic sclerosis (specifically, non-selective myeloablative HSCT versus cyclophosphamide; selective myeloablative HSCT versus cyclophosphamide; non-selective non-myeloablative HSCT versus cyclophosphamide).

SEARCH METHODS: We searched for randomized controlled trials (RCTs) in CENTRAL, MEDLINE, Embase, and trial registries from database insertion to 4 February …

Identification Of Therapeutic Targets For Th17 Cell-Mediated Diseases, Jin Wang

Theses and Dissertations (ETD)

Hypersensitivity and autoimmune diseases are complex synergistic effect of environmental, genetic and other factors. T helper 17 (Th17) cells play a critical role in the immune pathology. Th17 cells are a group of specialized CD4+ T cells with potential pro-inflammatory function which are different from other T cells such as T helper 1 (Th1) cells or T helper 2 (Th2) cells. Th17 cell development and differentiation processes are strictly regulated through complex pathways. Th17 cells are characterized by secreting cytokines such as IL-17 and IL-22. Studies have shown that Th17 cells and IL-17 have been implicated in the pathogenesis of …

Postoperative Major Adverse Cardiac Events In Patients With Systemic Lupus Erythematosus, Sebastian Bruera, Xiudong Lei, Brandon Blau, Hui Zhao, Anita Deswal, Jinoos Yazdany, Sharon H Giordano, Maria E Suarez-Almazor

Faculty, Staff and Students Publications

OBJECTIVES: Patients with systemic lupus erythematosus (SLE) have a high risk of cardiovascular disease that could potentially increase postoperative major adverse cardiac events (MACE). We determined the rate of MACE in patients with SLE undergoing noncardiac surgery using national claims-based data.

METHODS: This was a retrospective cohort study using Optum Clinformatics Data Mart from 2007 to 2020. We identified a cohort of patients with SLE who had undergone noncardiac surgeries using Current Procedural Terminology codes. We also identified two control cohorts without SLE, one with diabetes mellitus (DM) and one without DM. After matching cases and controls by age and …

Psychological Trauma Alters T-Lymphocyte Inflammation And Redox Through Sympathetic Mechanisms, Safwan K. Elkhatib

Theses & Dissertations

Posttraumatic stress disorder (PTSD) is a devastating psychiatric disorder characterized by distinctive symptom clusters, including intrusive memories (i.e., flashbacks), avoidance of related stimuli, affective changes, and hyperarousal. Strikingly, patients with PTSD face a significantly increased risk for a number of inflammation-driven pathologies, ranging from cardiovascular to autoimmune disease. Yet, the exact etiology of this increased risk remains unknown. The immune system is known to be strongly influenced by the sympathetic nervous system, and sympathetic overactivity is a hallmark of PTSD. Lymphoid organs, such as the spleen, are richly innervated by sympathetic nerve fibers which terminate near adaptive immune …

Evaluating The Validity Of Restrictions On Blood Donation Eligibility For Men Who Have Sex With Men (Msm) In The United States, France, And Switzerland, Swathi Gorantla

Independent Study Project (ISP) Collection

For the first time in a decade, the number of new human immunodeficiency virus (HIV) diagnoses is higher for heterosexual people compared to gay and bisexual men (Florêncio, 2022). Additionally, in the United States, the American Red Cross has declared a national blood crisis due to the nationwide shortage of donated blood. During this crisis, charged with the new information on HIV diagnosis rates, many advocates for the Lesbian, Gay, Bisexual, Transgender, Queer (LGBTQ+) community question why discriminatory policy surrounding gay and bisexual men donating still exist around the world. These policies are changing worldwide – several European countries have …

Variations In Antibody Response To Aspergillus Fumigatus Inhalation In Mice, Andrea Wells

Student Academic Conference

Studies have configured immunological responses to Aspergillus fumigatus in mice, leading to advanced understandings. However, the comparisons of the immune responses between juvenile (younger than 6 weeks) male and female C57BL/6J mice after A. fumigatus exposure, remains uninvestigated. In this study, we intranasally inoculated 3 week old male and female mice with Aspergillus fumigatus spores dilution of 2 106spores per 40 l. They were exposed to the allergen once a week for 8 consecutive weeks and euthanized on day 28 post the last inoculation. As compared to our last report, we increased the sample size for each group in this …

The Effects Of Glucocorticoids And Immunosuppressants On Cancer Outcomes In Checkpoint Inhibitor Therapy, Sebastian Bruera, Maria E Suarez-Almazor

Faculty, Staff and Students Publications

The emergence of checkpoint inhibitors has created a paradigm shift for the treatment of various malignancies. However, although these therapies are associated with improved survival rates, they also carry the risk of immune-related adverse events (irAEs). Moderate to severe irAEs are typically treated with glucocorticoids, sometimes with the addition of immunosuppressants as steroid-sparing therapy. However, it is unclear how glucocorticoids and immunosuppressants may impact cancer survival and the efficacy of immune checkpoint therapy on cancer. In this narrative review, we discuss the effects of glucocorticoids and immunosuppressants including methotrexate, hydroxychloroquine, azathioprine, mycophenolate mofetil, tumor-necrosis factor (TNF)-inhibitors, interleukin-6 inhibitors, interleukin-1 inhibitors, …

Apathy Is Not Associated With A Panel Of Biomarkers In Older Adults With Hiv Disease, Steven Paul Woods, Jennifer L Thompson, Michelle A Babicz, Lokesh Shahani, Gabriela Delevati Colpo, Natalia P Rocha, Erin E Morgan, Antonio L Teixeira

Faculty, Staff and Student Publications

OBJECTIVE: Apathy is prevalent in HIV disease and can significantly impact personal well-being; however, little is known about its neurobiological substrates in persons with HIV (PWH) disease.

METHODS: This cross-sectional, correlational study examined the association between apathy and several plasma biomarkers (tumor necrosis factor alpha, kynurenine, tryptophan, quinolinic acid, brain-derived neurotrophic factor, glial fibrillary acidic protein, neurofilament light chain, and phosphorylated tau at position threonine 181) in 109 PWH and 30 seronegative participants ages 50 and older. Apathy was measured with a composite score derived from subscales of the Frontal Systems Behavior Scale and the Profile of Mood States.

RESULTS: …

Multiple Sclerosis And Its Symptom Management Through Supplementation And Dietary Planning, Lindsey J. Davis

Selected Honors Theses

Multiple Sclerosis (MS) is an autoimmune, neuroinflammatory disorder that is characterized by the breakdown of myelinated axons in the Central and Peripheral Nervous Systems. It is a potentially debilitating autoimmune disease that affects almost 1 million people in the United States, and nearly 2.5 million people worldwide. The precise etiology of MS is still being researched, but much progress has been made towards understanding the molecular mechanisms and impactful ways to treat this disease. While there is still no cure, new treatment plans are constantly being orchestrated in effort to alleviate the burden that MS carries. Combination treatment plans have …

Acute Encephalitis, Myoclonus And Sweet Syndrome After Mrna-1273 Vaccine, Gabriel Torrealba-Acosta, Jennifer C Martin, Yve Huttenbach, Catherine R Garcia, Muhammad R Sohail, Sandeep Krishna Agarwal, Carina Wasko, Eric M Bershad, Mohammad I Hirzallah

Faculty, Staff and Students Publications

A patient presented with fever, generalised rash, confusion, orofacial movements and myoclonus after receiving the first dose of mRNA-1273 vaccine from Moderna. MRI was unremarkable while cerebrospinal fluid showed leucocytosis with lymphocyte predominance and hyperproteinorrachia. The skin evidenced red, non-scaly, oedematous papules coalescing into plaques with scattered non-follicular pustules. Skin biopsy was consistent with a neutrophilic dermatosis. The patient fulfilled the criteria for Sweet syndrome. A thorough evaluation ruled out alternative infectious, autoimmune or malignant aetiologies, and all manifestations resolved with glucocorticoids. While we cannot prove causality, there was a temporal correlation between the vaccination and the clinical findings.

Simian Varicella Virus Antibody Response In Recombinant Svv-Siv Immunized Primates, Kiser Horne

Honors Theses

Since its emergence in the early 1980’s HIV has killed approximately 32 million people, and continues to kill over half a million people every year. Significant research into potential vaccines and cures for HIV has been ongoing for decades but has been largely unsuccessful. One of the more promising technologies that is being investigated to develop an HIV vaccine is recombinant vaccine technology. The study presented in this thesis aims to use simian varicella virus (SVV) and simian immunodeficiency virus (SIV) to act as a model for recombinant vaccine development. If a recombinant SVV-SIV vaccine can be proven safe and …

Therapeutic Potential Of Trp Channels In The Targeting Of Rheumatoid Arthritis Synovial Fibroblasts, Brittany Isabella Schwam

Theses and Dissertations (ETD)

Rheumatoid arthritis is a chronic inflammatory disease primarily affecting the synovium, articular cartilage, and bone within a joint, but it is a unique form of arthritis wherein effects are systemic. The cause of this autoimmune disease remains unknown, but there are many environmental and genetic factors that play into susceptibility. Research is still far from drug-free remission despite great advancements over the past few decades. The majority of therapies developed rely on immunosuppressant or immunomodulator molecules and come with risk of infection, high costs, and toxic, uncontrolled side effects. Those diagnosed maintain a significant unmet need for targeted therapies.

There …

Intrapulmonary Administration Of Purified Neil2 Abrogates Nf-Κb-Mediated Inflammation, Nisha Tapryal, Shandy Shahabi, Anirban Chakraborty, Koa Hosoki, Maki Wakamiya, Gobinda Sarkar, Gulshan Sharma, Victor J Cardenas, Istvan Boldogh, Sanjiv Sur, Gourisankar Ghosh, Tapas K Hazra

Faculty, Staff and Students Publications

Aberrant or constitutive activation of nuclear factor kappa B (NF-κB) contributes to various human inflammatory diseases and malignancies via the upregulation of genes involved in cell proliferation, survival, angiogenesis, inflammation, and metastasis. Thus, inhibition of NF-κB signaling has potential for therapeutic applications in cancer and inflammatory diseases. We reported previously that Nei-like DNA glycosylase 2 (NEIL2), a mammalian DNA glycosylase, is involved in the preferential repair of oxidized DNA bases from the transcriptionally active sequences via the transcription-coupled base excision repair pathway. We have further shown that Neil2-null mice are highly sensitive to tumor necrosis factor α (TNFα)- and lipopolysaccharide-induced …

Development, Expansion And Role Of Myeloid-Derived Suppressor Cells In Post-Sepsis Immune Suppression, Tuqa Alkhateeb

Electronic Theses and Dissertations

Myeloid-derived suppressor cells (MDSCs) numbers increase significantly in sepsis and are associated with high mortality rates. These myeloid cell precursors promote immunosuppression, especially in the late (post sepsis) stage. However, the mechanisms that underlie MDSC expansion and programming are not completely understood. To investigate these mechanisms, we used a cecal-ligation and puncture (CLP) mouse model of polymicrobial sepsis that progresses from an early/acute proinflammatory phase to a late/chronic immunosuppressive phase. Previous studies in our laboratory showed that microRNA (miR)-21 and miR-181b elevate levels of the transcription factor nuclear factor 1 (NFI-A) that promotes MDSC expansion. We report here that miR-21 …

Molecular Mechanisms And Epidemiology Of Covid-19 From An Allergist’S Perspective, Koa Hosoki, Abhijit Chakraborty, Sanjiv Sur

Faculty, Staff and Students Publications

The global pandemic caused by the newly described severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused worldwide suffering and death of unimaginable magnitude from coronavirus disease 2019 (COVID-19). The virus is transmitted through aerosol droplets, and causes severe acute respiratory syndrome. SARS-CoV-2 uses the receptor-binding domain of its spike protein S1 to attach to the host angiotensin-converting enzyme 2 receptor in lung and airway cells. Binding requires the help of another host protein, transmembrane protease serine S1 member 2. Several factors likely contribute to the efficient transmission of SARS-CoV-2. The receptor-binding domain of SARS-CoV-2 has a 10- to 20-fold …