Digital Commons Network^™

Bisindolylmaleimide Ix: A Novel Anti-Sars-Cov2 Agent Targeting Viral Main Protease 3clpro Demonstrated By Virtual Screening Pipeline And In-Vitro Validation Assays, Yash Gupta, Dawid Maciorowski, Samantha E. Zak, Krysten A. Jones, Rahul S. Kathayat, Saara-Anne Azizi, Raman Mathur, Catherine M. Pearce, David J. Ilc, Hamza Husein, Andrew S. Herbert, Ajay Bharti, Brijesh Rathi, Ravi Durvasula, Daniel P. Becker, Bryan C. Dickinson, John M. Dye, Prakasha Kempaiah

Chemistry: Faculty Publications and Other Works

SARS-CoV-2, the virus that causes COVID-19 consists of several enzymes with essential functions within its proteome. Here, we focused on repurposing approved and investigational drugs/compounds. We targeted seven proteins with enzymatic activities known to be essential at different stages of the viral cycle including PLpro, 3CLpro, RdRP, Helicase, ExoN, NendoU, and 2′-O-MT. For virtual screening, energy minimization of a crystal structure of the modeled protein was carried out using the Protein Preparation Wizard (Schrodinger LLC 2020-1). Following active site selection based on data mining and COACH predictions, we performed a high-throughput virtual screen of drugs and investigational molecules (n = …

Mast Cell Activation Symptoms Are Prevalent In Long-Covid, Leonard B Weinstock, Jill B Brook, Arthur S Walters, Ashleigh Goris, Lawrence B Afrin, Gerhard J Molderings

Open Access Publications

OBJECTIVES: Hyper-inflammation caused by COVID-19 may be mediated by mast cell activation (MCA) which has also been hypothesized to cause Long-COVID (LC) symptoms. We determined prevalence/severity of MCA symptoms in LC.

METHODS: Adults in LC-focused Facebook support groups were recruited for online assessment of symptoms before and after COVID-19. Questions included presence and severity of known MCA and LC symptoms and validated assessments of fatigue and quality of life. General population controls and mast cell activation syndrome (MCAS) patients were recruited for comparison if they were ≥18 years of age and never had overt COVID-19 symptoms.

RESULTS: There were 136 …

Positron Emission Tomography In The Covid-19 Pandemic Era, Chentao Jin, Xiaoyun Luo, Shufang Qian, Kai Zhang, Yuanxue Gao, Rui Zhou, Peili Cen, Zhoujiao Xu, Hong Zhang, Mei Tian

Faculty, Staff and Student Publications

Coronavirus disease 2019 (COVID-19) has become a major public health problem worldwide since its outbreak in 2019. Currently, the spread of COVID-19 is far from over, and various complications have roused increasing awareness of the public, calling for novel techniques to aid at diagnosis and treatment. Based on the principle of molecular imaging, positron emission tomography (PET) is expected to offer pathophysiological alternations of COVID-19 in the molecular/cellular perspectives and facilitate the clinical management of patients. A number of PET-related cases and research have been reported on COVID-19 over the past one year. This article reviews the current studies of …

Hand Hygiene And Hospital-Acquired Infections During Covid-19 Increased Vigilance: One Hospital’S Experience, Alexander Kong, Carlos S. Botero Suarez, Bebe Rahamatalli, Jennifer Shankweiler, Olga Karasik

HCA Healthcare Journal of Medicine

Background

Hospital-acquired infections are associated with increased morbidity, mortality, costs and length of stay. Prior studies have linked increased hand hygiene compliance with reduced hospital-acquired infection rate. With the increased vigilance for personal and institutional hygiene practices during the COVID-19 pandemic, we hypothesized increased hand hygiene compliance and, as a result, decrease in hospital-acquired infections in our hospital.

Methods

Hand hygiene compliance data was provided by the hospital’s Quality Department. We queried and empirically analyzed local hospital-acquired infection data obtained from our Quality Department and the National Healthcare Safety Network. We compared local hand hygiene compliance rates before and after …

Laboratory Diagnostic Testing For Covid-19, Nuntra Suwantarat, Sidayu Suriya

Asian Medical Journal and Alternative Medicine

Laboratory tests play an important role for Corona Virus Disease 2019 (COVID-19) diagnosis. The diagnostic key point is an appropriate testing during the course of disease. In the early course of COVID-19 infection, nucleic acid amplification tests (NAATs) especially real-time reverse-transcription polymerase chain reaction (RT-PCR) of the respiratory specimen is the gold standard test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection due to the highest sensitivity and specificity during the first 2 weeks after the exposure. A rapid antigen test for SARS-CoV-2 has less complexity of the testing procedure and the faster TAT. However, a rapid antigen test …

Gastrointestinal And Liver Manifestations Of Covid-19, Keerati Kiattikunrat, Sith Siramolpiwat

Asian Medical Journal and Alternative Medicine

Almost every country in the world has been affected by the pandemic of Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), first reported in Wuhan, China, in December 2019. The clinical manifestation is diverse, ranging from asymptomatic to severe pneumonia requiring mechanical ventilation. In addition, gastrointestinal symptoms have also been reported to occur during the course of the disease. In some patients, gastrointestinal symptoms may precede respiratorytract symptoms. Interestingly, the SARS-CoV-2 RNA could be detected in the stool of COVID-19 patients, implying that SARS-CoV-2 may be transmitted by fecal-oral route. Moreover, mild transient abnormal liver …

Covid-19 In Children, Pornumpa Bunjoungmanee, Detchvijitr Suwanpakdee

Asian Medical Journal and Alternative Medicine

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a pandemic in many countries necessitating the employment of massive public health responses. Clinical manifestations of children with COVID-19 are typically less severe than adult patients. Most children with COVID-19 remain asymptomatic or become mildly symptomatic. However, children can also get severely ill from COVID-19. Infants who are under the age of one year and children with preexisting comorbidities may be more likely to develop severe illness and are at an increased risk for hospitalization and critical care. Rarely, COVID-19 may result in multisystem inflammatory syndrome …

Potential Thai Herbal Medicine For Covid-19, Arunporn Itharat, Vilailak Tiyao, Kodchanipha Sutthibut, Neal M. Davies

Asian Medical Journal and Alternative Medicine

SARS-CoV-2 is a cause of COVID-19 a contagious respiratory disease, in which there are many signs and symptoms such as fever, dry cough, shortness of breath, muscle ache, and pneumonia. Meanwhile, antiviral drug mechanisms which are being used to treat SARS-CoV-2 with Western drugs can be divided into three groups as follows: increasing acidic conditions by endosomal formation; viral replication; and affinity interaction with ACE-2 receptor via S-protein. Therefore, hydroxychloroquine/chloroquine, lopinavir, remdesivir, favipiravir, and molnupiravir which have been utilized to treat HIV and influenza via inhibiting viral replication and alkalinization could also modulate COVID-19 symptoms. However, antiviral drugs also have …

Current And Repurposing Medication For Sars-Cov-2 Infection, Kittiya Jantarathaneewat, Korakoch Kangwantas, Nattapong Tidwong

Asian Medical Journal and Alternative Medicine

In the crisis of COVID-19 pandemic, there is no specific agent to treat SARS-CoV-2 infection. Repurposing medication can be an alternative agent. Remdesivir is the first antiviral drug that has been approved for COVID-19 treatment whereas lopinavir/ritonavir and hydroxychloroquine, which was early used in SARS-CoV-2 widespread, are against by well-known guidelines due to lack of efficacy and potential toxicity. Corticosteroids are an essential supportive care in COVID-19 patient with severe disease to reduce lung inflammation. Favipiravir may have a potential benefit for COVID-19 patient, but the data is still uncertain. Ivermectin, an antihelmintic agent, may be used against SARS-CoV-2 but …

Covid-19 Treatment, Suttichai Visuttichaikit

Asian Medical Journal and Alternative Medicine

The ongoing outbreak of COVID-19 has posed a great threat to public health. The various degree and dynamic of illness severity, together with the fact that only few drugs have been proven as an effective therapy has created critical challenges in disease management. Patients in acute viral phase usually present with upper respiratory tract and/or gastrointestinal illness, fever, and myalgia. Antiviral therapy might provide the greatest benefit in reducing disease progression in such patients with older age or significant comorbidities while immunomodulators are less likely to provide advantages. Patients in immune dysregulation phase usually present with pneumonia of different severity. …

A Novel Class Of Tmprss2 Inhibitors Potently Block Sars-Cov-2 And Mers-Cov Viral Entry And Protect Human Epithelial Lung Cells, Matthew Mahoney, Vishnu C Damalanka, Michael A Tartell, Anne E Mayer Bridwell, Jorine Voss, Partha Karmakar, Paul W Rothlauf, Cassandra E Thompson, Christina L Stallings, Sean P J Whelan, James W Janetka, Et Al

Open Access Publications

The host cell serine protease TMPRSS2 is an attractive therapeutic target for COVID-19 drug discovery. This protease activates the Spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and of other coronaviruses and is essential for viral spread in the lung. Utilizing rational structure-based drug design (SBDD) coupled to substrate specificity screening of TMPRSS2, we have discovered covalent small-molecule ketobenzothiazole (kbt) TMPRSS2 inhibitors which are structurally distinct from and have significantly improved activity over the existing known inhibitors Camostat and Nafamostat. Lead compound MM3122 (4) has an IC

Integrin Activation Is An Essential Component Of Sars-Cov-2 Infection, Peter Simons, Derek A. Rinaldi, Virginie Bondu, Alison M. Kell, Steven Bradfute, Diane S. Lidke, Tione Buranda

Pathology Research and Scholarship

SARS-CoV-2 infection depends on binding its spike (S) protein to angiotensin-converting enzyme 2 (ACE2). The S protein expresses an RGD motif, suggesting that integrins may be co-receptors. Here, we UV-inactivated SARS-CoV-2 and fluorescently labeled the envelope membrane with octadecyl rhodamine B (R18) to explore the role of integrin activation in mediating cell entry and productive infection. We used flow cytometry and confocal microscopy to show that SARS-CoV-2^R18 particles engage basal-state integrins. Furthermore, we demonstrate that Mn2+, which induces integrin extension, enhances cell entry of SARS-CoV-2^R18. We also show that one class of integrin antagonist, which binds to …

University Of Louisville International Travel Clinic: Pivoting During The Covid-19 Pandemic, Dawn Balcom, Subathra Marimuthu, Leslie A Wolf, Luanne Didelot, Sarah Tan, Daniel Hall, Ruth Carrico

The University of Louisville Journal of Respiratory Infections

No abstract provided.

Long-Term Survival Of Older Patients Hospitalized For Covid-19. Do Clinical Characteristics Upon Admission Matter?, Michał Chojnicki, Agnieszka Neumann-Podczaska, Mikołaj Seostianin, Zofia Tomczak, Hamza Tariq, Jerzy Chudek, Sławomir Tobis, Iwona Mozer-Lisewska, Aleksandra Suwalska, Andrzej Tykarski, Piotr Merks, Sylwia Kropińska, Małgorzata Sobieszczańska, Frank Romanelli, Katarzyna Wieczorowska-Tobis

Pharmacy Practice and Science Faculty Publications

Older adults are particularly susceptible to COVID-19 in terms of both disease severity and risk of death. To compare clinical differences between older COVID-19 hospitalized survivors and non-survivors, we investigated variables influencing mortality in all older adults with COVID-19 hospitalized in Poznań, Poland, through the end of June 2020 (n = 322). In-hospital, post-discharge, and overall 180-day mortality were analyzed. Functional capacity prior to COVID-19 diagnosis was also documented. The mean age of subjects was 77.5 ± 10.0 years; among them, 191 were females. Ninety-five (29.5%) died during their hospitalization and an additional 30 (9.3%) during the post-discharge period …

Project Earthrise: Proceedings Of The Ninth Annual Conference Of Invivo Planetary Health, Susan L. Prescott, Ganesa Wegienka, Remco Kort, David H. Nelson, Sabine Gabrysch, Trevor Hancock, Anita Kozyrskyj, Christopher A. Lowry, Nicole Redvers, Blake Poland, Jake Robinson, Jean-Claude Moubarac, Sara Warber, Janet Jansson, Aki Sinkkonen, John Penders, Susan Erdman, Ralph Nanan, Matilda Van Den Bosch, Kirk Schneider, Nicholas J. Schroeck, Tanja Sobko, Jamie Harvie, George A. Kaplan, Rob Moodie, Laura Lengnick, Isaac Prilleltensky, Yuria Celidwen, Susan H. Berman, Alan C. Logan, Brian Berman

Public Health Sciences Articles

The "Earthrise" photograph, taken on the 1968 Apollo 8 mission, became one of the most significant images of the 20th Century. It triggered a profound shift in environmental awareness and the potential for human unity-inspiring the first Earth Day in 1970. Taking inspiration from these events 50 years later, we initiated

How Does A Medical Team In The Oncology Department React To The Covid-19 Pandemic?, Secil Omer, Andreea Maria Smarandache, Ioana Omer, Anda-Natalia Ciuhu, Roxana-Andreea Rahnea-Nita, Valentin-Titus Grigorean, Liliana Florina Andronache, Alexandru-Rares Stoian

Journal of Mind and Medical Sciences

The Covid-19 pandemic was and still is a great challenge for the entire world population. People in the first line, among them doctors being a very important category, faced the risk of disease and, in some cases, even became infected. The emotional consequences of this risk are highlighted in this paperwork which tries to stress, with the help of applied questionnaires, the presence of psycho-emotional disorders among the medical staff of the Oncology Department of St. Luke's Hospital, Bucharest, during the pandemic.

The medical staff had a low level of stress, adapting to the evolution of the pandemic "to some …

Stress And Anxiety Among Physicians And Nurses In Romania During The Covid-19 Pandemic, Romina-Marina Sima, Octavian-Gabriel Olaru, Anca Cazaceanu, Cristian Scheau, Mihai-Traian Dimitriu, Mihai Popescu, Liana Ples

Journal of Mind and Medical Sciences

Objective. This study aimed at identifying the stress and anxiety levels among physicians and nurses working in Romanian hospitals during the COVID-19 pandemic. Methods and Results. We conducted an online survey with a questionnaire completed by 169 healthcare providers aged between 25 and 69 years from COVID and non-COVID hospitals. There were 87.6% physicians and 12.4% nurses, with 61.5% women and 38.5% men. Clinicians experienced high levels of stress in 2.7% of the cases, medium stress in 68.9% of the cases, and low stress in 28.4% of the cases. Women experienced more stress (2.9% high level, 66.3% medium level) than …

Defining The Innate Immune Responses For Sars-Cov-2-Human Macrophage Interactions, Mai M. Abdelmoaty, Pravin Yeapuri, Jatin Machhi, Katherine E. Olson, Farah Shahjin, Vikas Kumar, You Zhou, Jingjing Liang, Kabita Pandey, Arpan Acharya, Siddappa N. Byrareddy, R. Lee Mosley, Howard E. Gendelman

Nebraska Center for Biotechnology: Faculty and Staff Publications

Host innate immune response follows severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and it is the driver of the acute respiratory distress syndrome (ARDS) amongst other inflammatory end-organ morbidities. Such life-threatening coronavirus disease 2019 (COVID-19) is heralded by virus-induced activation of mononuclear phagocytes (MPs; monocytes, macrophages, and dendritic cells). MPs play substantial roles in aberrant immune secretory activities affecting profound systemic inflammation and end-organ malfunctions. All follow the presence of persistent viral components and virions without evidence of viral replication. To elucidate SARS-CoV- 2-MP interactions we investigated transcriptomic and proteomic profiles of human monocyte-derived macrophages. While expression of the …

An Opportunistic Survey Reveals An Unexpected Coronavirus Diversity Hotspot In North America, Hon S. Ip, Kathryn M. Griffin, Jeffrey D. Messer, Megan E. Winzeler, Susan A. Shriner, Mary Lea Killian, Mia Kim Torchetti, Thomas J. Deliberto, Brian R. Amman, Caitlin M. Cossaboom, R. Reid Harvey, Natalie M. Wendling, Hannah Rettler, Dean Taylor, Jonathan S. Towner, Casey Barton Behravesh, David S. Blehert

United States Department of Agriculture Wildlife Services: Staff Publications

In summer 2020, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) was detected on mink farms in Utah. An interagency One Health response was initiated to assess the extent of the outbreak and included sampling animals from on or near affected mink farms and testing them for SARS-CoV-2 and non-SARS coronaviruses. Among the 365 animals sampled, including domestic cats, mink, rodents, raccoons, and skunks, 261 (72%) of the animals harbored at least one coronavirus. Among the samples that could be further characterized, 127 alphacoronaviruses and 88 betacoronaviruses (including 74 detections of SARS-CoV-2 in mink) were identified. Moreover, at least 10% (n …

High-Throughput Next-Generation Sequencing Respiratory Viral Panel: A Diagnostic And Epidemiologic Tool For Sars-Cov-2 And Other Viruses, Nikhil S. Sahajpal, Ashis K. Mondal, Allan Njau, Zachary Petty, Jiani Chen, Sudha Ananth, Pankaj Ahluwalia, Colin Williams, Ted M. Ross, Alka Chaubey

Pathology, East Africa

Two serious public health challenges have emerged in the current COVID-19 pandemic namely, deficits in SARS-CoV-2 variant monitoring and neglect of other co-circulating respiratory viruses. Additionally, accurate assessment of the evolution, extent, and dynamics of the outbreak is required to understand the transmission of the virus. To address these challenges, we evaluated 533 samples using a high-throughput next-generation sequencing (NGS) respiratory viral panel (RVP) that includes 40 viral pathogens. The performance metrics revealed a PPA, NPA, and accuracy of 95.98%, 85.96%, and 94.4%, respectively. The clade for pangolin lineage B that contains certain distant variants, including P4715L in ORF1ab, Q57H …

Fate And Transport Of The Microbiome In Built Environments, Dahae Seong

Theses and Dissertations

Buildings are complex ecosystems evolving continuously. Indoor components such as occupants, ventilation system, and building structures influence the microbiome. To shed light on how the microbial population in a building will respond to such a fluid system, the fundamental interactions between microbes and the indoor ecosystem must be understood. Buildings are being designed as air-tight structures to save energy; however, this could lead to degradation of indoor air quality through indoor sources of contaminants and/or containment of pollutants in the room or introduce outdoor pollutants indoors depending on the ventilation conditions. In addition, transmission of infectious microbes in indoors threaten …

Transmission Event Of Sars-Cov-2 Delta Variant Reveals Multiple Vaccine Breakthrough Infections, Timothy Farinholt, Harsha Doddapaneni, Xiang Qin, Vipin Menon, Qingchang Meng, Ginger Metcalf, Hsu Chao, Marie-Claude Gingras, Vasanthi Avadhanula, Paige Farinholt, Charu Agrawal, Donna M Muzny, Pedro A Piedra, Richard A Gibbs, Joseph Petrosino

Faculty, Staff and Students Publications

BACKGROUND: This study aims to identify the causative strain of SARS-CoV-2 in a cluster of vaccine breakthroughs. Vaccine breakthrough by a highly transmissible SARS-CoV-2 strain is a risk to global public health.

METHODS: Nasopharyngeal swabs from suspected vaccine breakthrough cases were tested for SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) by qPCR (quantitative polymerase chain reaction) for Wuhan-Hu1 and alpha variant. Positive samples were then sequenced by Swift Normalase Amplicon Panels to determine the causal variant. GATK (genome analysis toolkit) variants were filtered with allele fraction ≥80 and min read depth 30x.

RESULTS: Viral sequencing revealed an infection cluster of …

Preparing Nursing Homes For A Second Wave Of Coronavirus Disease 2019 (Covid-19), A Rekha Murthy, Hilary Babcock, Et Al.

2020-Current year OA Pubs

No abstract provided.

Persistence Of Post-Covid Lung Parenchymal Abnormalities During The Three-Month Follow-Up, Ali Bin Sarwar Zubairi, Anjiya Shaikh, Syed Muhammad Zubair, Akbar Shoukat Ali, Safia Awan, Muhammad Irfan

Section of Pulmonary & Critical Care

Introduction: COVID-19-associated pulmonary sequalae have been increasingly reported after recovery from acute infection. Therefore, we aim to explore the charactersitics of persistent lung parenchymal abnormalities in patients with COVID-19.
Material and methods: An observational study was conducted in patients with post-COVID lung parenchymal abnormalities from April till September 2020. Patients ≥18 years of age with COVID-19 who were diagnosed as post-COVID lung parenchymal abnormality based on respiratory symptoms and HRCT chest imaging after the recovery of acute infection. Data was recorded on a structured pro forma, and descriptive analysis was performed using Stata version 12.1.
Results: A total of 30 …

Clinical Outcomes In Patients Co-Infected With Covid-19 And Staphylococcus Aureus: A Scoping Review, Jenna Adalbert, Karan Varshney, Rachel Tobin, Rafael Pajaro

College of Population Health Faculty Papers

BACKGROUND: Endemic to the hospital environment, Staphylococcus aureus (S. aureus) is a leading bacterial pathogen that causes deadly infections such as bacteremia and endocarditis. In past viral pandemics, it has been the principal cause of secondary bacterial infections, significantly increasing patient mortality rates. Our world now combats the rapid spread of COVID-19, leading to a pandemic with a death toll greatly surpassing those of many past pandemics. However, the impact of co-infection with S. aureus remains unclear. Therefore, we aimed to perform a high-quality scoping review of the literature to synthesize the existing evidence on the clinical outcomes of COVID-19 …

In-Silico Analysis Of Protein Receptors Contributing To Sars- Cov-2 High Infectivity, Ismail Atia, Mohamed L Salem, Aya Elkholy, Wael Elmashad, Gomaa A. M. Ali

Information Sciences Letters

SARS-CoV-2 attacked more than 120 million people and causing the death of more than two million worldwide. Because of the crucial role of ACE2 protein as an entry for SRS-COV2, we investigated the proteins sequence in seventy- three living species. Data analysis of protein sequences, ACE2 mRNA, expression analysis, and protein interaction for humans and other living species were obtained from databases. The phylogenetic tree was constructed using MEGA6. We found 95% or more similarity between the conserved protein domains between Homo sapiens and Felis catus, Pan troglodytes, Pan paniscus, and Equus caballus. These species could be expressed the protein …

Pulmonary Inflammation And Injury Triggered By Spine Surgery In Recovered Covid-19 Patients Demand Consideration, Luciano Rodrigo Lopes, Silvana Kertzer Kasinski

The University of Louisville Journal of Respiratory Infections

No abstract provided.

Dna-Encoded Chemistry Technology Yields Expedient Access To Sars-Cov-2m Pro Inhibitors, Srinivas Chamakuri, Shuo Lu, Melek Nihan Ucisik, Kurt M Bohren, Ying-Chu Chen, Huang-Chi Du, John C Faver, Ravikumar Jimmidi, Feng Li, Jian-Yuan Li, Pranavanand Nyshadham, Stephen S Palmer, Jeroen Pollet, Xuan Qin, Shannon E Ronca, Banumathi Sankaran, Kiran L Sharma, Zhi Tan, Leroy Versteeg, Zhifeng Yu, Martin M Matzuk, Timothy Palzkill, Damian W Young

Faculty, Staff and Students Publications

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has killed more than 4 million humans globally, but there is no bona fide Food and Drug Administration–approved drug-like molecule to impede the COVID-19 pandemic. The sluggish pace of traditional therapeutic discovery is poorly suited to producing targeted treatments against rapidly evolving viruses. Here, we used an affinity-based screen of 4 billion DNA-encoded molecules en masse to identify a potent class of virus-specific inhibitors of the SARS-CoV-2 main protease (Mpro) without extensive and time-consuming medicinal chemistry. CDD-1714, the initial three-building-block screening hit (molecular weight [MW] = 542.5 g/mol), was a potent inhibitor (inhibition …

Dna-Encoded Chemistry Technology Yields Expedient Access To Sars-Cov-2m Pro Inhibitors, Srinivas Chamakuri, Shuo Lu, Melek Nihan Ucisik, Kurt M Bohren, Ying-Chu Chen, Huang-Chi Du, John C Faver, Ravikumar Jimmidi, Feng Li, Jian-Yuan Li, Pranavanand Nyshadham, Stephen S Palmer, Jeroen Pollet, Xuan Qin, Shannon E Ronca, Banumathi Sankaran, Kiran L Sharma, Zhi Tan, Leroy Versteeg, Zhifeng Yu, Martin M Matzuk, Timothy Palzkill, Damian W Young

Faculty, Staff and Students Publications

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has killed more than 4 million humans globally, but there is no bona fide Food and Drug Administration–approved drug-like molecule to impede the COVID-19 pandemic. The sluggish pace of traditional therapeutic discovery is poorly suited to producing targeted treatments against rapidly evolving viruses. Here, we used an affinity-based screen of 4 billion DNA-encoded molecules en masse to identify a potent class of virus-specific inhibitors of the SARS-CoV-2 main protease (Mpro) without extensive and time-consuming medicinal chemistry. CDD-1714, the initial three-building-block screening hit (molecular weight [MW] = 542.5 g/mol), was a potent inhibitor (inhibition …

Comprehensive Characterization Of Covid-19 Patients With Repeatedly Positive Sars-Cov-2 Tests Using A Large Us Electronic Health Record Database, Xiao Dong, Yujia Zhou, Xiao-Ou Shu, Elmer V Bernstam, Rebecca Stern, David M Aronoff, Hua Xu, Loren Lipworth

Faculty, Staff and Student Publications

In the absence of genome sequencing, two positive molecular tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) separated by negative tests, prolonged time, and symptom resolution remain the best surrogate measure of possible reinfection. Using a large electronic health record database, we characterized clinical and testing data for 23 patients with repeatedly positive SARS-CoV-2 PCR test results ≥60 days apart, separated by ≥2 consecutive negative test results. The prevalence of chronic medical conditions, symptoms, and severe outcomes related to coronavirus disease 19 (COVID-19) illness were ascertained. The median age of patients was 64.5 years, 40% were Black, and 39% …