Fast Funding for COVID-19 Science

Science funding mechanisms are too slow in normal times and may be much too slow during the COVID-19 pandemic. Fast Grants are an effort to correct this.

If you are a scientist at an academic institution currently working on a COVID-19 related project and in need of funding, we invite you to apply for a Fast Grant. Fast Grants are $10k to $500k and decisions are made in under 48 hours. If we approve the grant, you'll receive payment as quickly as your university can receive it.

Applications are paused

Due to receipt of a very large number of qualified submissions, Fast Grant applications are currently paused. If Fast Grants secures additional funding, we will resume issuing new grants. Sign up if you’d like to be notifed if we reopen applications:

The grants are currently supported by: Arnold Ventures, John Collison, Patrick Collison, Crankstart, Emerson Collective, Kim and Scott Farquhar, Paul Graham, Reid Hoffman, Fiona McKean and Tobias Lütke, Yuri and Julia Milner, Elon Musk, Chris and Crystal Sacca, Schmidt Futures, and others. AWS has contributed compute credits.

Fast Grants funders have committed over $22M to funding Fast Grant awardees. If you are an interested funder, please reach out: fund@fastgrants.org.

Who is eligible to apply for a Fast Grant?

You must be:

  • A PI at an academic institution;
  • Already working on a project that could help with the COVID-19 pandemic within the next six months;
  • In need of additional funding to complete the project.

Researchers outside the US are eligible for funding.

Why the six month constraint?

Most existing funding bodies focus on supporting longer-term work. Given COVID-19’s human costs, speed is of paramount importance.

Who will make grant decisions?

A panel of biomedical scientists will make funding recommendations to Emergent Ventures.

What can a Fast Grant be used for?

We require that a Fast Grant be used solely to expedite COVID-19-related science. Beyond that, the grant recipient has complete discretion over how it is spent.

What criteria will panelists use?

We’ll prefer projects that are cheap (so that our fund dollars go further) and that will yield results quickly (during COVID-19, days matter).

Does the grant go to the PI or to the university?

This is at the discretion of the applicant.

When can I apply?

Fast Grants open at 12:00 Pacific Time on Tuesday, April 7, 2020. We will wait until Sunday, April 12 before we award our first grants in order to give our reviewers time to calibrate. Subsequent decisions will be made within 48 hours. (That is: applications submitted before April 12 will be reviewed within the 48 hours following April 12.)

What conditions apply?

  • You must use the grant to work on COVID-19-related science.
  • For six months, you must send us monthly updates, summarizing your progress. These updates can be as simple as a single-paragraph email.
  • You must upload all manuscripts reporting work supported by the grant to a preprint server such as bioRxiv or arXiv upon submission to a peer-reviewed journal.
  • In line with Gates Foundation policy, will pay at most 10% in overhead costs to the university.

How do IP rights work?

Apart from the open science publication requirement above, there are no IP restrictions associated with Fast Grants.

Who administers Fast Grants?

Fast Grants is a part of Emergent Ventures, a project at the Mercatus Center at George Mason University. For Canadian recipients, Fast Grants makes funding recommendations to the Thistledown Foundation.

Are contributions to Fast Grants tax deductible?

Yes, the Mercatus Center, of which Fast Grants/Emergent Ventures is a part, is a 501c(3) organization.

Will the identities of grant recipients be made public?

This shall be at the recipient's discretion. We will list those who agree to be named. We will also provide regular updates on the total dollars that have been allocated.

What inspired Fast Grants?

During World War II, the NDRC accomplished a lot of research very quickly. In his memoir, Vannevar Bush recounts: “Within a week NDRC could review the project. The next day the director could authorize, the business office could send out a letter of intent, and the actual work could start.” Fast Grants are an effort to unlock progress at a cadence similar to that which served us well then.

Grant recipients

The list below is updated regularly with additional recipients. As of May 9th, 127 awards have been made. Not all recipients are currently listed.

Addgene

For continuing to share critical reagents with researchers at minimal cost during the Covid-19 pandemic.

Dr. Patricia Aguilar
University of Texas

For modeling age-dependent susceptibility to SARS-CoV-2 infection in 3D human lung organoids.

Dr. Hector Aguilar-Carreno
Cornell University

To use a novel viral membrane inhibitor to produce a SARS-CoV-2 vaccine

Dr. Wataru Akahata
Kyoto University

For the development of a Covid-19 vaccine specificially targeted to the receptor-binding domain of the viral S protein using expertise gained during successful development of anti-malaria and anti-chikungunya vaccines.

Dr. James Antaki
Cornell University

For the collaborative effort with Accel Diagnostics to develop a point of care serological test for rapid quantification of antibody titer to monitor disease progression and strength of immune response.

Dr. Susan Athey
Stanford University

For retrospective analyses designed to assess the benefit of off-label drug use, in order to help prioritize and guide subsequent randomized clinical trials.

Dr. Michael Barry
Mayo Clinic

For the development of a single-cycle adenovirus vaccine and viral decoy against SARS-CoV-2.

Dr. Mark Bathe
MIT

For a collaborative effort with the Lingwood and Schmidt labs combining vaccine immunology and nanotechnology expertise to rapidly test and characterize COVID-19 vaccine candidates in high-throughput.

Dr. John Bell
Ottawa Hospital Research Institute

To create multiple vaccines for COVID-19 using novel strategies for delivering coronavirus proteins directly to the critical cells required to generate an effective immune response.

Dr. Carolyn Bertozzi
Stanford University

For a collaboration of Dr. Carolyn Bertozzi, Dr. Catherine Blish and Dr. Marie Hollenhorst to identify minimally invasive predictive biomarkers for Covid-19 disease progression to improve scarce resource allocation.

Dr. Lbachir BenMohamed
UC Irvine

For the development of an asymptomatic multi-epitope COVID-19 vaccine.

Dr. Catherine Blish
Stanford University

To determine best practices for N95 mask decontamination that will sufficiently inactivate virus and allow mask reuse in a clinical setting

Dr. Jeff Biernaskie
University of Calgary

To study the immune basis of COVID-19 related acute respiratory distress syndrome (ARDs) via longitudinal study of patients undergoing placebo and convalescent plasma treatment in order to inform evidence-based repurposing of targeted immunotherapies to improve outcomes for critically-ill patients affected by COVID-19.

Dr. Pamela Bjorkman
Caltech

For electron tomography imaging of SARS-CoV-2 virions trapped in the act of fusion by novel fusion inhibitors

Dr. Jim Boonyaratanakornkit
Fred Hutchinson Cancer Research Center

To probe the human B cell repertoire for SARS-CoV-2-protective B cells from pre-immune individuals in order to guide vaccine and monoclonal antibody design against COVID-19.

Dr. Gillian Booth
University of Toronto

To accelerate the CONNECT study (COVID-19 and diabetes: Clinical Outcomes and Navigated NEtwork Care Today) to define the relationship between diabetes and adverse COVID-19 outcomes and improve care for individuals with diabetes.

Dr. Stephen Brohawn
UC Berkeley

To develop novel COVID-19 therapeutics that target coronavirus ion channels in collaboration with the Bautista and Adesnik labs.

Dr. J. Brian Byrd
University of Michigan Medical School

To support a randomized, controlled clinical trial testing whether continuation, or discontinuation of two common types of blood pressure medication leads to better outcomes in patients hospitalized with COVID-19.

Dr. Ann Chahroudi
Emory University School of Medicine

To investigate cross-reactive, cross-neutralizing, and antibody-dependent enhancing (ADE) antibodies of circulating endemic coronaviruses.

Dr. Amy Chung
University of Melbourne

To accelerate the characterization of antibodies from COVID19 patients that are associated with rapid recovery compared to severe disease; and to identify potent monoclonal antibodies capable of inhibiting the virus, which will be prioritized for therapeutic development

Dr. Susan Daniel
Cornell University

To investigate the impact of FDA-approved calcium-modulating drugs on lessening COVID infection, based on their work identifying a role for calcium ions in virus entry.

Dr. Brandon J. DeKosky
The University of Kansas

For high-throughput screening of antibody responses in COVID-19 patients for therapeutic discovery and to accelerate vaccine design.

Dr. Shokrollah Elahi
University of Alberta

Understanding the immune correlates of protection in infected individuals with a mild form of COVID-19 versus those with the severe form of the disease is essential for therapeutic interventions or vaccine design.

Dr. John Eikelboom
McMaster University

For the ACT program design using innovative and adaptive methodology to find a safe, effective treatment to slow the progression of COVID-19 across 80 sites in 8 countries over 6 months.

Dr. Barbara Engelhardt
Princeton University

For creating a national database of COVID+ patient data and studying it to gain a better understanding of disease trajectory, improved hospital resource allocation and the acceleration of clinical trials.

Dr. Laura Esserman
UCSF

For the ‘I-SPY for COVID-19’ Platform Trial to Reduce Mortality and Ventilator requirements for critically ill patient in collaboration with Dr. Carolyn Calfee and Dr. Kathleen Liu.

Dr. Tracy Fisher
Tulane University

To investigate the pathogenesis of COVID-19 in the development of a relevant animal model in order to advance our understanding of the disease process and for safe and efficacious therapeutic and vaccine development.

Dr. Steven Marc Friedman
University Health Network, University of Toronto

For a comparative study to validate saliva as a test for SARS-CoV-2, as an alternative to nasopharyngeal swab testing and its associated problems, including depletion of swabs and personal protective equipment, and risk of nosocomial infection from close proximity of health care worker and patient being tested

Dr. Judith Frydman
Stanford University

For using their combined expertise in virology and in multisubunit protein production to engineer virus-like particles (VLPs), which will allow for rapid testing of the neutralization capacity of recovered patient sera (in collaboration with the Blish lab) or designed antibodies targeting the S protein (in collaboration with the Wells lab).

Dr. Patrick Giguère
University of Ottawa

For the discovery of CoV-2 particle entry in absence of ACE2 and genome-wide gain-of-function screening to identify new secondary receptors/co-receptors/auxiliary proteins that facilitate viral entry/fusion.

Dr. Douglas Goetz
Ohio University

To determine the potential of GSK-3 inhibitors to diminish the cytokine storm associated with COVID-19.

Dr. Ewan Goligher
University Health Network and University of Manitoba

To support the Antithrombotic Therapy to Ameliorate Complications of COVID-19 (ATTACC) trial. This international, multicenter, adaptive, open-label randomized clinical trial will examine the impact of therapeutic anticoagulation in comparison to standard venous thromboprophylaxis on the risk of intubation and death in hospitalized patients with COVID-19.

Dr. Brigitte Gomperts
UCLA

For using a 3D human lung organoid model that is infected with SARS-CoV-2 to screen for new therapies to treat COVID19 and reduce lung injury.

Dr. Nathan Grubaugh
Yale School of Public Health

For developing new testing strategies and utilizing virus genomic sequencing to support data-driven decision making.

Dr. Jeremy Hirota
McMaster University

To correlate host transcriptome profile from clinical nasal swabs from positive and negative COVID-19 cases with clinical outcomes

Dr. Shirley Hsin-Ju Mei
Ottawa Hospital Research Institute

For the TURQUOISE Ottawa COVID-19 study profiling immune responses of COVID-19 patients admitted to the intensive care unit (ICU), with a focus on the potential immunomodulatory function of mesenchymal stem cells.

Dr. Eva Harris
UC Berkeley

To perform a randomized, representative, community-based, longitudinal study of short and long-term spread, asymptomatic infection rates, disease risk modifying factors and effects of non-pharmacological interventions for COVID-19 in the Bay Area.

Dr. Patrick Hsu
UC Berkeley

For the discovery of diagnostic and actionable biomarkers of COVID-19.

Dr. Akiko Iwasaki
Yale University

To elucidate the single cell transcriptional profiles of infected tissues from COVID-19 patients.

Dr. Smita Iyer
UC Davis

To investigate convalescent plasma therapy for COVID-19 in a rhesus model.

Dr. Peter K. Jackson
Stanford University School of Medicine

For elucidating a newly discovered mechanism by which the SARS-CoV-2 virus binds to its receptor(s) on trachea and nasal epithelium and defining a new drug target to block viral uptake and spread.

Dr. Jingyue Ju
Columbia University

To rapidly research and develop nucleotide analogues that inhibit SARS-CoV-2 polymerase as therapeutics for COVID-19.

Dr. Naftali Kaminski
Yale University

To perform a clinical trial assessing the efficacy of sobetirome in reducing the requirements for mechanical ventilation and mortality of moderate to severe hospitalized COVID-19 patients.

Dr. Kevin Kain
University Health Network

For a three-month multi-site randomized double-blind placebo-controlled study to assess safety and efficacy of hydroxy-chloroquine (HCQ) Pre-exposure Prophylaxis (PrEP) in the prevention of COVID-19 infections in high-risk Health Care Workers.

Dr. Yoshihiro Kawaoka
Influenza Research Institute, School of Veterinary Medicine, University of Wisconsin-Madison

Development of Syrian Hamsters as a Covid-19 model to test the Protective Efficacy of a Whole-Inactivated Vaccine.

Dr. Michael Kay
University of Utah

To discover and characterize novel D-peptide viral entry inhibitors as drug candidates to prevent and treat COVID-19.

Dr. Nevan Krogan
UCSF

For identifying SARS-CoV-2-Human Protein-Protein Interactions and evaluating them as potential therapeutic targets.

Dr. Ronald Levy
Stanford University

To generate a vaccine against SARS-CoV-2 using a novel polymer for mRNA protection.

Dr. Michael Lin
Stanford University

For developing a live-cell test for the activity of a key protein from SARS-CoV-2, the COVID-19 virus, and testing of a set of existing drugs for ability to disrupt this protein’s function.

Dr. Mark R. Looney
UCSF

To explore the pathogenic role of neutrophil extracellular traps (NETs) in COVID-19 by testing a strategy to dismantle NETs using a novel therapeutic to ameliorate acute lung injury.

Dr. Jonathon Maguire
University of Toronto

For the COVID-19 Study of Children and Families, a longitudinal observational study to evaluate the key epidemiological characteristics and spectrum of disease severity of COVID-19 among parents and children.

Dr. Rajeev Malhotra
Massachusetts General Hospital

To identify novel risk factors that determine which COVID-19 patients are at highest risk (e.g., those needing ICU care or to be on a ventilator) or who develop cardiac injury, with a particular focus on baseline vascular abnormalities.

Dr. Amanda J. Martinot
Tufts University Cummings School of Veterinary Medicine

For comparison of pre-clinical animal models for vaccine and therapeutic development and the basic immunology and virulence determinants underlying host-pathogen interactions.

Dr. Grant McFadden
Arizona State University

To develop a live intranasal COVID-19 vaccine to generate both humoral (especially respiratory mucosal) and cellular acquired immune responses against SARS-CoV-2, based on a recombinant version of an attenuated nonhuman poxvirus called myxoma virus that has been engineered to co-express the four SARS-CoV-2 proteins (S, N, M and E) needed to produce secreted non-infectious virus-like particles that antigenically mimic the complete SARS CoV-2 virus.

Dr. Allison McGeer
Sinai Health System

To test whether exististing antivirals can be used to control outbreaks of COVID-19 in nursing homes.

Dr. Roman Melnyk
University of Toronto and The Hospital for Sick Children

For high-throughput screening of repurposed FDA-approved drugs for their efficacy to prevent SARS-CoV2 entry by modifying endosomal pH and testing in preclinical hamster and ferret models of Covid-19 in collaboration with the Kozak and Falzarano labs.

Dr. Miriam Merad
Mount Sinai Medical Center

To comprehensively characterize the immunological response to SARS-CoV-2 and identify the factors that control the severity of COVID-19 disease based on a comprehensive and longitudinal COVID-19 BioBank of Mount Sinai’s very large COVID-19 patient population.

Dr. Edward Mills
McMaster University

To summarize rapidly emerging clinical research evidence and generate comparative efficacy and safety profiles for candidate interventions.

Dr. Keith Mostov
UCSF

To develop recombinant secretory immunoglobulin A antibodies to the SARS CoV-2 virus and use them to provide passive protection against infection.

Dr. Anders Näär
UC Berkeley

To develop anti-viral COVID-19 therapeutics based on direct targeting of the viral RNA genome using LNA anti-sense oligonucleotides.

Dr. Mihai Netea
Radboud University Medical Center

To support a randomized clinical trial to investigate whether vaccination with BCG is able to decrease the incidence and severity of COVID-19 infection in elderly individuals.

Dr. Daniel Nomura
UC Berkeley

For a collaborative effort of the Nomura, Murthy, Cate, Schaletzky, and Stanley labs to develop small molecule Covid-19 antivirals drugs.

Center for Open Science

To accelerate COVID-19 research by improving transparency of related registrations, data, materials, and preprints on the Open Science Framework (OSF.io) for discovery and consumption by researchers and other services.

Dr. Elizabeth L. Ogburn
Johns Hopkins School of Public Health

For developing the COVID Collaboration Platform to bring disparate research teams working on the same clinical research questions together to share protocols, data, and evidence. Outside of a few centrally organized trials, most COVID-19 randomized clinical trials are small and/or redundant—and it's only by aggregating evidence across these trials that we will learn how to best treat COVID-19.

Dr. Chul Park
University of Toronto

To cost-effectively modify N95 grade (and non-N95 grade) mask surfaces from hydrophilic (to which respiratory aerosols/droplets adhere) to hydrophobic (repelling respiratory aerosols/droplets), to increase their lifespan.

Dr. Jerry Pelletier
McGill University

To identify the most potent compound from a class of rocaglates for activity against SARS-CoV-2. Our previous work has shown that these compounds are effective against the non-pathogenic coronavirus 229E strain.

Dr. Bradley Pentelute
MIT

To develop safe and effective peptides for prophylactic treatment and rapid early therapeutic intervention against COVID-19 infection.

Dr. Nikolai Petrovsky
Flinders University

For a phase 1 clinical trial to test the efficacy of a recombinant protein-based Sars-CoV vaccine with Advax-SM adjuvant, based on expertise gained during SARS-CoV vaccine development.

Dr. Dylan Pillai
University of Calgary

To further develop a clinically validated COVID diagnostic point-of-care test.

Dr. Hidde Ploegh
Harvard University

To pursue targeted delivery of Covid-19 coronavirus antigens to antigen presenting cells in the form of nanobody-antigen adducts in the presence of approved adjuvants to elicit protective B- and T-cell (inluding CD8) responses as a possible vaccine strategy.

Dr. Angela Rasmussen
Columbia University

For the longitudinal study of COVID-19 progression in non-human primate models to identify potential disease-modifying pathways.

Dr. Brian Raught
University Health Network

To use two cutting-edge screening technologies to identify new drug targets for the treatment of COVID-19, and the identification of FDA-approved drugs with activity against SARS-CoV-2.

Dr. Jeffrey Ravetch
The Rockefeller University

To develop human ACE2 transgenic mice in strains that express all classes of human FcγRs to study the mechanisms of antibody-mediated protection against Covid-19 infection.

Dr. Davide F. Robbiani
The Rockefeller University

To rapidly identify a human monoclonal antibody that potently neutralizes SARS-CoV-2 and that is suitable for clinical development for prevention and treatment of COVID-19 based on convalescent serum screening.

Dr. Erica Ollmann Saphire
La Jolla Institute for Immunology

To scale up protein production in order to compare and advance antibody therapeutics against COVID-19 around the world through our international consortium.

Dr. Ansuman Satpathy
Stanford University

To identify the cellular and molecular basis for durable immunity to SARS-CoV-2, with a focus on the identification of T cell receptor and antibody sequences that are shared among virus controllers and the identification of immune dysfunction in COVID-19 that could be treated with existing FDA-approved drugs.

Dr. Jacqueline Saw
Vancouver General Hospital

For evaluating the use of cardiac CT angiography (CCTA) to study myocardial injury in COVID-19 patients.

Dr. Julia Schaletzky
UC Berkeley

Dr. Julia Schaletzky, Prof. Sarah Stanley and their team at the UCB Drug Discovery center work on a repurposing approach, discovering if compounds with existing safety data in humans can be used to combat COVID-19 infection.

Dr. Katherine Seley-Radtke
University of Maryland

The Seley-Radtke group has developed a series of flexible nucleoside analogues ("fleximers") that have exhibited potent activity against epidemic (i.e. SARS and MERS), and endemic (i.e., NL63) human coronaviruses (CoVs). The Fast Grant will help advance our synthetic efforts as well as to fastrack our preclinical animal studies against SARS-CoV-2 and CoVID-19.

Dr. Sachdev Sidhu
University of Toronto

For the discovery of human antibodies blocking ACE2 binding by the viral S protein through screening of libraries of billions of human antibodies and their further validation to move them towards clinical trials as an antiviral drug to fight COVID-19 directly.

Dr. Matthew Spitzer
UCSF

For discerning immune cell signaling states associated with disease escalation in COVID-19 based on prospective patient samples in order to identify therapeutic targets to modulate inflammation in COVID-19 patients.

Dr. Sarah Stanley
UC Berkeley

For testing of repurposed antiviral compounds in an in-vivo disease model.

Dr. Erec Stebbins
German Cancer Research Center

To create a COVID-19 vaccine through a novel immunotherapeutic platform.

Dr. Alice Ting
Stanford University

For the development of non-PCR point-of-care tests for COVID-19 infection, based on engineered peroxidase reporters.

Dr. Alain Townsend
Oxford University

To characterize monoclonal antibodies to Spike protein of SARS-CoV-2 from convalescent human donors for their binding, neutralization and structural properties.

Dr. Bert Vogelstein
Johns Hopkins University

Clinical trials to determine whether prazosin, a drug already widely used for common medical conditions, can prevent cytokine storms and severe disease in COVID-19 patients when given early after infection.

Dr. Arthur Wallace
UCSF and San Francisco VA Medical Center

To investigate ACE-I, ARB and type 5 PDE-I drugs in the context of ARDS and microvascular dysfunction in Covid-19 patients.

Dr. Taia Wang
Stanford University

Wang and her group are studying molecules that correlate with immunity against COVID-19. Their studies focus on defining a protective antibody response, and they will investigate whether antibodies have a role in determining the severity of COVID-19. The overarching goal of this work is to guide the development of vaccines and monoclonal antibody therapeutics against SARS-CoV-2.

Dr. Tania Watts
University of Toronto

To investigate the the diversity and longevity of T cell immunity to SARS-COV2 through longitudinal study of Covid-19 patients.

Dr. Craig Wilen
Yale University

To use state-of-the-art technologies including organoid culture and single-cell sequencing to identify the cell types infected by SARS-CoV2 and to reveal how the virus disturbs these cells to cause disease.

Dr. Paul Yager
University of Washington

For developing an isothermal point of care diagnostic test to detect Sars-CoV2.

Dr. Michael Yin
Columbia University

To investigate the relationship between systemic exposure to hydroxychloroquine and therapeutic efficacy as well as side effects in COVID-19 patients.

Dr. Qian Zhang
The Rockefeller University

For the global COVID Human Genetic Effort, to search for monogenic etiologies for rare individuals naturally resistant to SARS-CoV-2 infections, as well as young and previously healthy individuals who suffered from life-threatening COVID-19.

Papers published by Fast Grants recipients

A mouse-adapted SARS-CoV-2 model for the evaluation of COVID-19 medical countermeasures

Kenneth H. Dinnon, Sarah R. Leist, Alexandra Schäfer, Caitlin E. Edwards, David R. Martinez, Stephanie A. Montgomery, Ande West, Boyd L. Yount Jr, Yixuan J. Hou, Lily E. Adams, Kendra L. Gully, Ariane J. Brown, Emily Huang, Matthew D. Bryant, Ingrid C. Choong, Jeffrey S. Glenn, Lisa E. Gralinski, Timothy P. Sheahan, Ralph S. Baric

Abstract

Coronaviruses are prone to emergence into new host species most recently evidenced by SARSCoV-2, the causative agent of the COVID-19 pandemic. Small animal models that recapitulate SARS-CoV-2 disease are desperately needed to rapidly evaluate medical countermeasures (MCMs). SARS-CoV-2 cannot infect wildtype laboratory mice due to inefficient interactions between the viral spike (S) protein and the murine ortholog of the human receptor, ACE2. We used reverse genetics to remodel the S and mACE2 binding interface resulting in a recombinant virus (SARS-CoV-2 MA) that could utilize mACE2 for entry. SARS-CoV-2 MA replicated in both the upper and lower airways of both young adult and aged BALB/c mice. Importantly, disease was more severe in aged mice, and showed more clinically relevant phenotypes than those seen in hACE2 transgenic mice. We then demonstrated the utility of this model through vaccine challenge studies in immune competent mice with native expression of mACE2. Lastly, we show that clinical candidate interferon (IFN) lambda-1a can potently inhibit SARS-CoV-2 replication in primary human airway epithelial cells in vitro, and both prophylactic and therapeutic administration diminished replication in mice. Our mouse-adapted SARS-CoV-2 model demonstrates age-related disease pathogenesis and supports the clinical use of IFN lambda-1a treatment in human COVID-19 infections

A SARS-CoV-2 protein interaction map reveals targets for drug repurposing

David E. Gordon, Gwendolyn M. Jang, Mehdi Bouhaddou, Jiewei Xu, Kirsten Obernier, Kris M. White, Matthew J. O’Meara, Veronica V. Rezelj, Jeffrey Z. Guo, Danielle L. Swaney, Tia A. Tummino, Ruth Huettenhain, Robyn M. Kaake, Alicia L. Richards, Beril Tutuncuoglu, Helene Foussard, Jyoti Batra, Kelsey Haas, Maya Modak, Minkyu Kim, Paige Haas, Benjamin J. Polacco, Hannes Braberg, Jacqueline M. Fabius, Manon Eckhardt, Margaret Soucheray, Melanie J. Bennett, Merve Cakir, Michael J. McGregor, Qiongyu Li, Bjoern Meyer, Ferdinand Roesch, Thomas Vallet, Alice Mac Kain, Lisa Miorin, Elena Moreno, Zun Zar Chi Naing, Yuan Zhou, Shiming Peng, Ying Shi, Ziyang Zhang, Wenqi Shen, Ilsa T. Kirby, James E. Melnyk, John S. Chorba, Kevin Lou, Shizhong A. Dai, Inigo Barrio-Hernandez, Danish Memon, Claudia Hernandez-Armenta, Jiankun Lyu, Christopher J. P. Mathy, Tina Perica, Kala B. Pilla, Sai J. Ganesan, Daniel J. Saltzberg, Ramachandran Rakesh, Xi Liu, Sara B. Rosenthal, Lorenzo Calviello, Srivats Venkataramanan, Jose Liboy-Lugo, Yizhu Lin, Xi-Ping Huang, YongFeng Liu, Stephanie A. Wankowicz, Markus Bohn, Maliheh Safari, Fatima S. Ugur, Cassandra Koh, Nastaran Sadat Savar, Quang Dinh Tran, Djoshkun Shengjuler, Sabrina J Fletcher, Michael C. O’Neal, Yiming Cai, Jason C. J. Chang, David J. Broadhurst, Saker Klippsten, Phillip P. Sharp, Nicole A. Wenzell, Duygu Kuzuoglu, Hao-Yuan Wang, Raphael Trenker, Janet M. Young, Devin A. Cavero, Joseph Hiatt, Theodore L. Roth, Ujjwal Rathore, Advait Subramanian, Julia Noack, Mathieu Hubert, Robert M. Stroud, Alan D. Frankel, Oren S. Rosenberg, Kliment A Verba, David A. Agard, Melanie Ott, Michael Emerman, Natalia Jura, Mark von Zastrow, Eric Verdin, Alan Ashworth, Olivier Schwartz, Christophe d’Enfert, Shaeri Mukherjee, Matt Jacobson, Harmit S. Malik, Danica G. Fujimori, Trey Ideker, Charles S. Craik, Stephen N. Floor, James S. Fraser, John D. Gross, Andrej Sali, Bryan L. Roth, Davide Ruggero, Jack Taunton, Tanja Kortemme, Pedro Beltrao, Marco Vignuzzi, Adolfo García-Sastre, Kevan M. Shokat, Brian K. Shoichet & Nevan J. Krogan

Abstract

The novel coronavirus SARS-CoV-2, the causative agent of COVID-19 respiratory disease, has infected over 2.3 million people, killed over 160,000, and caused worldwide social and economic disruption1,2. There are currently no antiviral drugs with proven clinical efficacy, nor are there vaccines for its prevention, and these efforts are hampered by limited knowledge of the molecular details of SARS-CoV-2 infection. To address this, we cloned, tagged and expressed 26 of the 29 SARS-CoV-2 proteins in human cells and identified the human proteins physically associated with each using affinity-purification mass spectrometry (AP-MS), identifying 332 high-confidence SARS-CoV-2-human protein-protein interactions (PPIs). Among these, we identify 66 druggable human proteins or host factors targeted by 69 compounds (29 FDA-approved drugs, 12 drugs in clinical trials, and 28 preclinical compounds). Screening a subset of these in multiple viral assays identified two sets of pharmacological agents that displayed antiviral activity: inhibitors of mRNA translation and predicted regulators of the Sigma1 and Sigma2 receptors. Further studies of these host factor targeting agents, including their combination with drugs that directly target viral enzymes, could lead to a therapeutic regimen to treat COVID-19.

Considering BCG vaccination to reduce the impact of COVID-19

Nigel Curtis, Annie Sparrow, Tedros A Ghebreyesus, Mihai G Netea

Abstract

The novel coronavirus SARS-CoV-2, the causative agent of COVID-19 respiratory disease, has infected over 2.3 million people, killed over 160,000, and caused worldwide social and economic disruption1,2. There are currently no antiviral drugs with proven clinical efficacy, nor are there vaccines for its prevention, and these efforts are hampered by limited knowledge of the molecular details of SARS-CoV-2 infection. To address this, we cloned, tagged and expressed 26 of the 29 SARS-CoV-2 proteins in human cells and identified the human proteins physically associated with each using affinity-purification mass spectrometry (AP-MS), identifying 332 high-confidence SARS-CoV-2-human protein-protein interactions (PPIs). Among these, we identify 66 druggable human proteins or host factors targeted by 69 compounds (29 FDA-approved drugs, 12 drugs in clinical trials, and 28 preclinical compounds). Screening a subset of these in multiple viral assays identified two sets of pharmacological agents that displayed antiviral activity: inhibitors of mRNA translation and predicted regulators of the Sigma1 and Sigma2 receptors. Further studies of these host factor targeting agents, including their combination with drugs that directly target viral enzymes, could lead to a therapeutic regimen to treat COVID-19.

COVID-19 and emerging viral infections: The case for interferon lambda

Ludmila Prokunina-Olsson, Noémie Alphonse, Ruth E. Dickenson, Joan E. Durbin, Jeffrey S. Glenn, Rune Hartmann, Sergei V. Kotenko, Helen M. Lazear, Thomas R. O’Brien, Charlotte Odendall, Olusegun O. Onabajo, Helen Piontkivska, Deanna M. Santer, Nancy C. Reich, Andreas Wack, Ivan Zanoni

Abstract

With the first reports on coronavirus disease 2019 (COVID-19), which is caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the scientific community working in the field of type III IFNs (IFN-λ) realized that this class of IFNs could play an important role in this and other emerging viral infections. In this Viewpoint, we present our opinion on the benefits and potential limitations of using IFN-λ to prevent, limit, and treat these dangerous viral infections.

Saliva is more sensitive for SARS-CoV-2 detection in COVID-19 patients than nasopharyngeal swabs

Anne Louise Wyllie, John Fournier, Arnau Casanovas-Massana, Melissa Campbell, Maria Tokuyama, Pavithra Vijayakumar, Bertie Geng, M. Catherine Muenker, Adam J. Moore, Chantal B. F. Vogels, Mary E. Petrone, Isabel M. Ott, Peiwen Lu, Alice Lu-Culligan, Jonathan Klein, Arvind Venkataraman, Rebecca Earnest, Michael Simonov, Rupak Datta, Ryan Handoko, Nida Naushad, Lorenzo R. Sewanan, Jordan Valdez, Elizabeth B. White, Sarah Lapidus, Chaney C. Kalinich, Xiaodong Jiang, Daniel J. Kim, Eriko Kudo, Melissa Linehan, Tianyang Mao, Miyu Moriyama, Ji Eun Oh, Annsea Park, Julio Silva, Eric Song, Takehiro Takahashi, Manabu Taura, Orr-El Weizman, Patrick Wong, Yexin Yang, Santos Bermejo, Camila Odio, Saad B. Omer, Charles S. Dela Cruz, Shelli Farhadian, Richard A. Martinello, Akiko Iwasaki, Nathan D. Grubaugh, Albert I. Ko

Abstract

Rapid and accurate SARS-CoV-2 diagnostic testing is essential for controlling the ongoing COVID-19 pandemic. The current gold standard for COVID-19 diagnosis is real-time RT-PCR detection of SARS-CoV-2 from nasopharyngeal swabs. Low sensitivity, exposure risks to healthcare workers, and global shortages of swabs and personal protective equipment, however, necessitate the validation of new diagnostic approaches. Saliva is a promising candidate for SARS-CoV-2 diagnostics because (1) collection is minimally invasive and can reliably be self-administered and (2) saliva has exhibited comparable sensitivity to nasopharyngeal swabs in detection of other respiratory pathogens, including endemic human coronaviruses, in previous studies. To validate the use of saliva for SARS-CoV-2 detection, we tested nasopharyngeal and saliva samples from confirmed COVID-19 patients and self-collected samples from healthcare workers on COVID-19 wards. When we compared SARS-CoV-2 detection from patient-matched nasopharyngeal and saliva samples, we found that saliva yielded greater detection sensitivity and consistency throughout the course of infection. Furthermore, we report less variability in self-sample collection of saliva. Taken together, our findings demonstrate that saliva is a viable and more sensitive alternative to nasopharyngeal swabs and could enable at-home self-administered sample collection for accurate large-scale SARS-CoV-2 testing.

Preventing cytokine storm syndrome in COVID-19 using α-1 adrenergic receptor antagonists

Maximilian F. Konig, Michael A. Powell, Verena Staedtke, Ren-Yuan Bai, David L. Thomas, Nicole M. Fischer, Sakibul Huq, Adham M. Khalafallah, Allison Koenecke, Ruoxuan Xiong, Brett Mensh, Nickolas Papadopoulos, Kenneth W. Kinzler, Bert Vogelstein, Joshua T. Vogelstein, Susan Athey, Shibin Zhou, and Chetan Bettegowda

Abstract

Rapid and accurate SARS-CoV-2 diagnostic testing is essential for controlling the ongoing COVID-19 pandemic. The current gold standard for COVID-19 diagnosis is real-time RT-PCR detection of SARS-CoV-2 from nasopharyngeal swabs. Low sensitivity, exposure risks to healthcare workers, and global shortages of swabs and personal protective equipment, however, necessitate the validation of new diagnostic approaches. Saliva is a promising candidate for SARS-CoV-2 diagnostics because (1) collection is minimally invasive and can reliably be self-administered and (2) saliva has exhibited comparable sensitivity to nasopharyngeal swabs in detection of other respiratory pathogens, including endemic human coronaviruses, in previous studies. To validate the use of saliva for SARS-CoV-2 detection, we tested nasopharyngeal and saliva samples from confirmed COVID-19 patients and self-collected samples from healthcare workers on COVID-19 wards. When we compared SARS-CoV-2 detection from patient-matched nasopharyngeal and saliva samples, we found that saliva yielded greater detection sensitivity and consistency throughout the course of infection. Furthermore, we report less variability in self-sample collection of saliva. Taken together, our findings demonstrate that saliva is a viable and more sensitive alternative to nasopharyngeal swabs and could enable at-home self-administered sample collection for accurate large-scale SARS-CoV-2 testing.