Virus Diseases Commons^™

Timing Of Invasive Mechanical Ventilation And Death In Critically Ill Adults With Covid-19: A Multicenter Cohort Study., Adam Green, Jean-Sebastien Rachoin, Christa Schorr, Phil Dellinger, Jonathan D Casey, Isabel Park, Shruti Gupta, Rebecca M Baron, Shahzad Shaefi, Krystal Hunter, David E Leaf

Cooper Medical School of Rowan University Departmental Research

PURPOSE: To investigate if the timing of initiation of invasive mechanical ventilation (IMV) for critically ill patients with COVID-19 is associated with mortality.

MATERIALS AND METHODS: The data for this study were derived from a multicenter cohort study of critically ill adults with COVID-19 admitted to ICUs at 68 hospitals across the US from March 1 to July 1, 2020. We examined the association between early (ICU days 1-2) versus late (ICU days 3-7) initiation of IMV and time-to-death. Patients were followed until the first of hospital discharge, death, or 90 days. We adjusted for confounding using a multivariable Cox …

The Interaction Between Host G3bp And Viral Nucleocapsid Protein Regulates Sars-Cov-2 Replication, Zemin Yang

Theses and Dissertations (ETD)

G3BP1/2 are RNA-binding proteins that promote condensation to form stress granules in response to various cellular stresses, including viral infection. G3BP1/2 are prominent interactors of the nucleocapsid (N) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the functional consequences of the G3BP-N interaction in the context of viral infection have remained unclear. Here we used structural and biochemical analyses to define the residues required for G3BP1-N interaction, followed by structure-guided mutagenesis of G3BP1 and N to selectively disrupt their interaction. We found that mutation of N-F17 led to selective loss of interaction with G3BP1 and consequent failure of …

Whole Body Cryotherapy As A Novel Treatment For Long Covid Syndrome Associated Brain Fog, James Mack, Brandon Goodwin, Paras Patel, Kyra Herman, Daniel Casal, Emily Levenson

Rowan-Virtua Research Day

SARS-CoV-2, which causes coronavirus disease 2019 (COVID-19), was first discovered in December 2019 in Wuhan, China when adults began presenting with severe pneumonia of an unknown cause. SARS-CoV-2 can cause a wide range of clinical manifestations. SARS-CoV-2 can penetrate the olfactory mucosa and may enter the brain through the cribriform plate along the olfactory tract, through vagal or trigeminal pathways, or pass through the blood-brain barrier. Once inside the brain, levels of inflammatory cytokines are increased and can lead to altered learning, memory, neuroplasticity, hallucinations, nightmares, cognitive and attention deficits, new-onset anxiety and depression, and psychosis. A theoretical treatment for …

An Interesting Occurrence Of Bell’S Palsy With Atypical Presentation After Contracting Covid-19 Infection, Yen-Chung Wang, Yen-Hsiang Wang, Christian Sanchez

North Texas GME Research Forum 2023

Introduction: COVID-19 has been identified as primarily a respiratory illness, however, with its clinical manifestation of involvement with multiple organs, it is now considered a systemic illness. In particular, it also can elicit a broad spectrum of neurological symptoms. One of the proposed manifestations is Bell’s Palsy, an acute idiopathic facial nerve palsy that affects the lower motor neuron. Here we have a patient with recent COVID infection who presents with a unilateral facial droop along with unilateral weakness/tingling of extremities and was diagnosed with Bell’s Palsy.

Case Description: Patient is a 47-year-old male with a past medical history of …

Acute Thalamic Stroke In A Covid Positive Adult: A Case Report, Norberto Escobales, Daniel Kiehl, Michelle Militello, Aleger Vorbes

South Atlantic Division GME Research Day 2023

No abstract provided.

Exploring The Possible Phenomenon Of Viral Interference Between The Novel Coronavirus And Common Respiratory Viruses, Spencer Deleveaux, Alexandria Clarke-Kregor, Xavier Fonseca-Fuentes, Essam Mekhaiel

Journal of Patient-Centered Research and Reviews

At the peak of the 2021 wave of the SARS-CoV-2 alpha variant in North America, there was concern for a superimposed wave of viral respiratory infections. There was, however, an apparent shift in the usual epidemiology of these pathogens, especially during the traditional influenza season from approximately October 2020 to March 2021. This article seeks to briefly describe the epidemiology of notable respiratory pathogens during the first wave of the COVID-19 pandemic and to focus on one possible factor for the trends observed. There are many contributory elements to the observed viral trends, but in particular, we present a synopsis …

Performance Of A Sars-Cov-2 Rt-Pcr Assay With Non-Traditional Specimen Types, Subathra Marimuthu, Holly Aliesky, Heather Ness, Daniya Sheikh, Sathya Rashmit, Dawn Balcom, Leslie A. Wolf

The University of Louisville Journal of Respiratory Infections

During the first two years of the coronavirus disease 2019 (COVID-19) pandemic, nasopharyngeal (NP) specimens were the gold standard for clinical diagnostic testing. As information about the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing the pandemic continued to be shared, it was clear that the virus could be detected in other specimen types during an active infection. The University of Louisville Infectious Diseases Laboratory accepted non-traditional specimen types, most without a paired, positive NP result, for research purposes only to support local epidemiology efforts. A real-time reverse transcription-polymerase chain reaction (RT-PCR) assay originally validated for NP specimens was used …

Endogenous Mirna-Based Innate-Immunity Against Sars-Cov-2 Invasion Of The Brain, Walter J. Lukiw, Aileen I. Pogue

School of Medicine Faculty Publications

The severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2), the causative agent of COVID-19, possesses an unusually large positive-sense, single-stranded viral RNA (ssvRNA) genome of about ~29,903 nucleotides (nt). In many respects, this ssvRNA resembles a very large, polycistronic messenger RNA (mRNA) possessing a 5′-methyl cap (m7GpppN), a 3′- and 5′-untranslated region (3′-UTR, 5′-UTR), and a poly-adenylated (poly-A+) tail. As such, the SARS-CoV-2 ssvRNA is susceptible to targeting by small non-coding RNA (sncRNA) and/or microRNA (miRNA), as well as neutralization and/or inhibition of its infectivity via the human body’s natural complement of about ~2650 miRNA species. Depending on host cell and tissue …

Analysis Of 3.5 Million Sars-Cov-2 Sequences Reveals Unique Mutational Trends With Consistent Nucleotide And Codon Frequencies, Sarah E. Fumagalli, Nigam H. Padhiar, Douglas Meyer, Upendra Katneni, Haim Bar, Michael Dicuccio, Anton A. Komar, Chava Kimchi‑Sarfaty

Biological, Geological, and Environmental Faculty Publications

Background: Since the onset of the SARS-CoV-2 pandemic, bioinformatic analyses have been performed to understand the nucleotide and synonymous codon usage features and mutational patterns of the virus. However, comparatively few have attempted to perform such analyses on a considerably large cohort of viral genomes while organizing the plethora of available sequence data for a month-by-month analysis to observe changes over time. Here, we aimed to perform sequence composition and mutation analysis of SARS-CoV-2, separating sequences by gene, clade, and timepoints, and contrast the mutational profile of SARS-CoV-2 to other comparable RNA viruses.Methods: Using a cleaned, filtered, and pre-aligned dataset …

Development Of A Novel Mathematical Model That Explains Sars-Cov-2 Infection Dynamics In Caco-2 Cells, Vladimir Staroverov, Stepan Nersisyan, Alexei Galatenko, Dmitriy Alekseev, Sofya Lukashevich, Fedor Ployakov, Nikita Anisimov, Alexander Tonevitsky

COVID-19 Papers, Posters, and Presentations

Mathematical modeling is widely used to study within-host viral dynamics. However, to the best of our knowledge, for the case of SARS-CoV-2 such analyses were mainly conducted with the use of viral load data and for the wild type (WT) variant of the virus. In addition, only few studies analyzed models for in vitro data, which are less noisy and more reproducible. In this work we collected multiple data types for SARS-CoV-2-infected Caco-2 cell lines, including infectious virus titers, measurements of intracellular viral RNA, cell viability data and percentage of infected cells for the WT and Delta variants. We showed …

Autonomic Function Recovery And Physical Activity Levels In Post-Covid-19 Young Adults After Immunization: An Observational Follow-Up Case-Control Study, Ana Paula Coelho Figueira Freire, Shaan Amin, Fabio Santos Lira, Ana Elisa Von Ah Morano, Telmo Pereira, Manuel-João Coelho-E-Silva, Armando Caseiro, Diego Giulliano Destro Christofaro, Vanessa Ribeiro Dos Santos, Osmar Marchioto Júnior, Ricardo Aurino Pinho, Bruna Spolador De Alencar Silva

All Faculty Scholarship for the College of Education and Professional Studies

Coronavirus disease 2019 (COVID-19) has detrimental multi-system consequences. Symptoms may appear during the acute phase of infection, but the literature on long-term recovery of young adults after mild to moderate infection is lacking. Heart rate variability (HRV) allows for the observation of autonomic nervous system (ANS) modulation post-SARS-CoV-2 infection. Since physical activity (PA) can help improve ANS modulation, investigating factors that can influence HRV outcomes after COVID-19 is essential to advancements in care and intervention strategies. Clinicians may use this research to aid in the development of non-medication interventions. At baseline, 18 control (CT) and 20 post-COVID-19 (PCOV) participants were …

Implementation Of Mrsa Nasal Swabs As An Antimicrobial Stewardship Intervention To Decrease Anti-Mrsa Therapy In Covid-19 Infection, Alaina Dekerlegand, Emily Johnston, Britney Mellor, Melanie Rae Schrack, Catherine O’Neal

School of Medicine Faculty Publications

In the early stages of treating patients with SARS-CoV-2, limited information was available to guide antimicrobial stewardship interventions. The COVID-19 Task Force and Antimicrobial Stewardship Committee, at a 988-bed academic medical center, implemented the use of methicillin-resistant Staphylococcus aureus (MRSA) nasal swab polymerase chain reaction (PCR) testing to assist with the de-escalation of anti-MRSA therapy in patients with suspected superimposed bacterial pneumonia in COVID-19. A retrospective study was conducted to evaluate the impact of MRSA nasal swab PCR testing on the rate of anti-MRSA therapy between 13 April 2020 and 26 July 2020. A total of 122 patients were included …

Outcomes Of Patients With Copd During The Covid Pandemic, Jacob Hentges, Julia Fashner

East Florida Division GME Research Day 2023

A scoping review of COVID-19's impact on healthcare delivery and health outcomes found disruptions in care delivery and a shift towards telemedicine(1). Another study found no significant change in the length of stay for patients admitted to the hospital for COPD exacerbation during the pandemic period compared to the pre-pandemic period(2).

We conducted a secondary analysis of HCA Florida St. Lucie Hospital data to compare the outcomes of patients with COPD before (Jan 2018 – Feb 2020) and during the COVID-19 pandemic (March 2020 – Dec 2021). The data included patients aged over 18 years who were diagnosed with COPD …

Covid-19 Vaccination And Alcohol Consumption: Justification Of Risks, Pavel A. Solopov

Bioelectrics Publications

Since the beginning of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, pharmaceutical companies and research institutions have been actively working to develop vaccines, and the mass roll-out of vaccinations against COVID-19 began in January 2021. At the same time, during lockdowns, the consumption of alcoholic beverages increased. During the peak of vaccination, consumption remained at high levels around the world, despite the gradual relaxation of quarantine restrictions. Two of the popular queries on search engines were whether it is safe to drink alcohol after vaccination and whether this will affect the effectiveness of vaccines. Over the past two …

New Onset Hashimoto’S Thyroiditis Associated With Severe Rhabdomyolysis After Infection With Covid19, Nova Mebane, Jacqueline M. Phillips, Cynthia Salloum, Neva Mebane, Daniel Park

Gulf Coast Division GME Research Day 2023

No abstract provided.

Generation Of Chimeric Rhinoviruses Presenting Sars-Cov-2 Broadly Neutralizing Epitopes And Their Antigenicity Characterization, Danish Ansari

Biotechnology Theses

The global COVID pandemic is not yet fully under control as there were over 21 million new cases of SARS-CoV-2 infections and over 50,000 deaths globally as of January of 2022. A heavily mutated variant of concern, Omicron is responsible for most of these cases which demands an urgency for a new vaccine. NIH reports over 180 vaccine candidates that use various strategies currently in development. However, a recurring concern with these vaccines is that the continuous viral mutations decrease the efficacy of vaccines. Therefore, we proposed to construct a human rhinovirus (HRV) based chimeric virus containing highly conserved, broadly …

Corrigendum: Evolution, Ecology, And Zoonotic Transmission Of Betacoronaviruses: A Review, Herbert F. Jelinek, Mira Mousa, Eman Alefishat, Wael Osman, Ian Spence, Dengpan Bu, Samuel F. Feng, Jason Byrd, Paola A. Magni, Shafi Sahibzada, Guan K. Tay, Habiba S. Alsafar

Research outputs 2022 to 2026

In the published article, there was an error in the legend for Figure 1 as published. The figure legend did not indicate that it has been adapted from Plowright et al. (2017). Copyright permission was obtained from Springer Nature to adapt Figure 1 from Plowright et al. (2017). The corrected legend appears below. Figure 1. Zoonotic risk distribution, pathway to spillover, and the multimodal role of the determinants of spillover. The zoonotic risk is demonstrated by the accumulated distribution of reservoir hosts and vectors that play a role in the pathway to spillover. The risk of spillover is determined by …

The Prevalence Of Sars-Cov-2 Antibodies Within The Community Of A Private Tertiary University In The Philippines: A Serial Cross Sectional Study, Lourdes S. Tanchanco, Jenica Clarisse Y. Sy, Angel Belle C. Dy, Myla D. Levantino, Arianna Maever L. Amit, John Wong, Kirsten Angeles, John Paul Vergara

Ateneo School of Medicine and Public Health Publications

The COVID-19 pandemic has caused a public health emergency in all sectors of society, including universities and other academic institutions. This study determined the seroprevalence of SARS-CoV-2 antibodies among administrators, faculty, staff, and students of a private tertiary academic institution in the Philippines over a 7 month period. It employed a serial cross-sectional method using qualitative and quantitative COVID-19 antibody test kits. A total of 1,318 participants were tested, showing 47.80% of the study population yielding IgG antibodies to SARS-CoV-2 virus. A general increase in seroprevalence was observed from June to December 2021, which coincided with the vaccine roll-out of …

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 …

A Phase 1a/1b Clinical Trial Design To Assess Safety, Acceptability, Pharmacokinetics And Tolerability Of Intranasal Q-Griffithsin For Covid-19 Prophylaxis, Henry W. Nabeta, Maryam Zahin, Joshua L. Fuqua, Elizabeth D. Cash, Ingrid Leth, Michael Strauss, Jeanne Novak, Lin Wang, Angela Siegwald, Rachel A. Sheppard, Shesh N. Rai, Lisa C. Rohan, Sharon Hillier, Gerald W. Dryden, Kevin L. Potts, Kenneth E. Palmer

The University of Louisville Journal of Respiratory Infections

Background: The COVID-19 pandemic remains an ongoing threat to global public health. Q-Griffithsin (Q-GRFT) is a lectin that has demonstrated potent broad-spectrum inhibitory activity in preclinical studies in models of Nipah virus and the beta coronaviruses SARS-CoV, MERS-CoV, and SARS-CoV-2.

Methods: Here, we propose a clinical trial design to test the safety, pharmacokinetics (PK), and tolerability of intranasally administered Q-GRFT for the prevention of SARS-CoV-2 infection as a prophylaxis strategy. The initial Phase 1a study will assess the safety and PK of a single dose of intranasally administered Q-GRFT. If found safe, the safety, PK, and tolerability of multiple doses …

Sars-Cov-2 Spike Conformation Determines Plasma Neutralizing Activity Elicited By A Wide Panel Of Human Vaccines, John E. Bowen, Young-Jun Park, Cameron Stewart, Jack T. Brown, William K. Sharkey, Alexandra C. Walls, Anshu Joshi, Kumail Ahmed, Asefa Shariq, Najeeha Talat Iqbal

Department of Paediatrics and Child Health

Numerous safe and effective coronavirus disease 2019 vaccines have been developed worldwide that use various delivery technologies and engineering strategies. We show here that vaccines containing prefusion-stabilizing S mutations elicit antibody responses in humans with enhanced recognition of S and the S1 subunit relative to postfusion S as compared with vaccines lacking these mutations or natural infection. Prefusion S and S1 antibody binding titers positively and equivalently correlated with neutralizing activity, and depletion of S1-directed antibodies completely abrogated plasma neutralizing activity. We show that neutralizing activity is almost entirely directed to the S1 subunit and that variant cross-neutralization is mediated …

Factors Associated With Loss Of Motivation And Hesitation To Work Amongst Frontline Health Care Providers During The Covid-19 Pandemic: A Cross-Sectional Survey From A Developing Country, Mehreen Malik, Syeda Tayyaba Rehan, Farheen Malik, Jawad Ahmed, Chaudhary Abdul Fatir, Hassan Ul Hussain, Asiyah Aman, Muhammad Junaid Tahir

Department of Anaesthesia

Background: The COVID-19 took over the world in 2020 and a lockdown has been imposed seeing its fast spread. Frontline health care workers (HCWs) were reported frequently with a lack of motivation, hesitancy and unwillingness to perform their duties during this pandemic. This cross-sectional survey aims to evaluate the factors associated with lack of motivation and increased hesitancy among the frontline HCWs to perform their duties during COVID-19 pandemic.
Materials and methods: A total of 239 HCWs were included in this web-based cross-sectional study, who have worked during the COVID-19 pandemic. The anonymous online questionnaire was sent to all faculty, …

Omicron Variants Of The Sars-Cov-2: A Potentially Significant Threat In A New Wave Of Infections, Lukasz Szarpak, Michal Pruc, Alla Navolokina, Kavita Batra, Francesco Chirico, Charles De Roquetaillade

School of Medicine Faculty Research

From the beginning, the COVID-19 pandemic turned out to be a huge challenge and burden for medical services [1]. Currently, humanity is dealing with a new wave of the virus that has evolved and presents a new challenge, mainly due to its ability to avoid immune surveillance. Indeed, our main line of defense — vaccines — may be compromised. Omicron variants are characterized by an evolutionary force unprecedented so far. Among the several sublines that have already emerged, the BA.5 strain exhibit higher transmissibility and demonstrates a worrisome immune evasion. According to several laboratory investigations, vaccination-induced antibodies are less successful …

Sars-Cov-2 Invasion And Pathological Links To Prion Disease, Walter J. Lukiw, Vivian R. Jaber, Aileen I. Pogue, Yuhai Zhao

School of Medicine Faculty Publications

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the COVID-19 disease, is a highly infectious and transmissible viral pathogen that continues to impact human health globally. Nearly ~600 million people have been infected with SARS-CoV-2, and about half exhibit some degree of continuing health complication, generically referred to as long COVID. Lingering and often serious neurological problems for patients in the post-COVID-19 recovery period include brain fog, behavioral changes, confusion, delirium, deficits in intellect, cognition and memory issues, loss of balance and coordination, problems with vision, visual processing and hallucinations, encephalopathy, encephalitis, neurovascular or cerebrovascular insufficiency, and/or …

Menstrual Irregularities Following Covid-19 Vaccination: A Global Cross-Sectional Survey, Azza Sarfraz, Zouina Sarfraz, Muzna Sarfraz, Zainab Nadeem, Miguel Felix, Ivan Cherrez-Ojeda

Department of Paediatrics and Child Health

Introduction: The coronavirus disease 2019 (COVID-19) vaccination generates protective immunity against SARS-CoV-2 infection. There is no clear evidence of COVID-19 vaccine-induced menstrual irregularities.
Objective: To identify potential menstrual irregularities following COVID-19 vaccine among females.
Methods: A worldwide cross-sectional survey study was conducted from June 10, 2021, to July 10, 2021 using online mediums. The survey consisted of 15 questions divided into baseline characteristics, vaccination status and dosage, menstruation and relate factors, and thoughts and knowledge about menstrual irregularities. Non-probability convenience sampling method was used including 510 responses. The results were tabulated, with bivariate analysis and chi-square test results. The sensitivity …

Igg Antibodies To Sars-Cov-2 In Asymptomatic Blood Donors At Two Time Points In Karachi, Muhammad Hasan, Bushra Moiz, Shama Qaiser, Kiran I. Masood, Zara Ghous, Areeba Hussain, Natasha Bahadur Ali, Syed Hani Abidi, Kulsoom Ghias, Erum Khan, Zahra Hasan

Department of Pathology and Laboratory Medicine

Introduction: An estimated 1.5 million cases were reported in Pakistan until 23 March, 2022. However, SARS-CoV-2 PCR testing capacity has been limited and the incidence of COVID-19 infections is unknown. Volunteer healthy blood donors can be a control population for assessment of SARS-CoV-2 exposure in the population. We determined COVID-19 seroprevalence during the second pandemic wave in Karachi in donors without known infections or symptoms in 4 weeks prior to enrollment.
Materials and methods: We enrolled 558 healthy blood donors at the Aga Khan University Hospital between December 2020 and February 2021. ABO blood groups were determined. Serum IgG reactivity …

Omicron Spike Function And Neutralizing Activity Elicited By A Comprehensive Panel Of Vaccines, John E. Bowen, Amin Addetia, Ha V Dang, Cameron Stewart, Jack T. Brown, William K. Sharkey, Kaitlin R. Sprouse, Kumail Ahmed, Asefa Shariq Ansari, Najeeha Talat Iqbal

Department of Paediatrics and Child Health

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant of concern comprises several sublineages, with BA.2 and BA.2.12.1 having replaced the previously dominant BA.1 and with BA.4 and BA.5 increasing in prevalence worldwide. We show that the large number of Omicron sublineage spike mutations leads to enhanced angiotensin-converting enzyme 2 (ACE2) binding, reduced fusogenicity, and severe dampening of plasma neutralizing activity elicited by infection or seven clinical vaccines relative to the ancestral virus. Administration of a homologous or heterologous booster based on the Wuhan-Hu-1 spike sequence markedly increased neutralizing antibody titers and breadth against BA.1, BA.2, BA.2.12.1, BA.4, and …

Implementation Of Multi-Level Interventions To Mitigate Risk Of Sars-Cov-2 Delta Variant At A Public University In Southern United States, Keena N. Arbuthnot, Rebecca C. Christofferson, Edward J. Trapido, John H. Pardue, John N. Perret, William F. Tate

School of Public Health Faculty Publications

During the coronavirus disease 2019 (COVID-19) pandemic, navigating the implementation of public health measures in a politically charged environment for a large state entity was challenging. However, Louisiana State University (LSU) leadership developed and deployed an effective, multi-layered mitigation plan and successfully opened in-person learning while managing cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during the fourth surge. We describe the plan to provide a framework for other institutions during this and future responses. The goals were 3-fold: maintain a quality learning environment, mitigate risk to the campus community, and ensure that LSU operations did not contribute to …

What About Anosmia From Covid-19 ?, Sharanya S E Santhi, Sara Elnour, Steven B Lippmann

The University of Louisville Journal of Respiratory Infections

No abstract provided.

Gain-Of-Signal Assays For Probing Inhibition Of Sars-Cov-2 Mpro/3clpro In Living Cells, Seyed Arad Moghadasi, Morgan A Esler, Yuka Otsuka, Jordan T Becker, Sofia N Moraes, Constance B Anderson, Srinivas Chamakuri, Christopher Belica, Chloe Wick, Daniel A Harki, Damian W Young, Louis Scampavia, Timothy P Spicer, Ke Shi, Hideki Aihara, William L Brown, Reuben S Harris

Faculty, Staff and Students Publications

The main protease, Mpro, of SARS-CoV-2 is required to cleave the viral polyprotein into precise functional units for virus replication and pathogenesis. Here, we report quantitative reporters for Mpro function in living cells in which protease inhibition by genetic or chemical methods results in robust signal readouts by fluorescence (enhanced green fluorescent protein [eGFP]) or bioluminescence (firefly luciferase). These gain-of-signal systems are scalable to high-throughput platforms for quantitative discrimination between Mpro mutants and/or inhibitor potencies as evidenced by validation of several reported inhibitors. Additional utility is shown by single Mpro amino acid variants and structural information combining to demonstrate that …