SARS-CoV-2 Updates – Therapeutics

VeroScience, Erasmus, MC, Rotterdam, Netherlands, Marion Koopmans

Scientific advisor The WHO R&D Blueprint and GLOPID-R

• VeroScience has isolates and cell-line cultures
• COVID-19 Global reference database in zoonotic & emerging viruses and 800+ hospitals network. Samples from different human coronaviruses patients of previous years.
• COVID-19 animal infection experiments-pathogenesis and transmissibility
• Patient enrollment for clinical trials; Animal vaccine evaluation and therapeutic antibody studies.

https://www.biorxiv.org/content/10.1101/2020.03.17.995639v1

 

University of Buffalo, Buffalo, New York, Gene Morse   

• Preliminary animal model studies-Lopinavir-ritonavir and Tocilizumab-Il-6 blocker
• Assays-Centers in Jamaica and Zimbabwe for screening approaches
• Collaborations: Pharma-antiviral INDs & NIAID: Remdesivir & IgM
• Develop regional early-warning strategies-Covid-19
• In-vitro antiviral testing, link observed activity of compounds with repurposing software at
• University of Buffalo that searches existing databases for similar structures
• Template phase | protocol for rapid transition from pre-clinical to clinical studies?
• mAB from recovering individuals be modeled to our current HIV-1-bNAb translational research protocols

http://medicine.buffalo.edu/covid-19.html

Global Biolife, Inc., David Ostrov, University of Southern Florida, USA

• Compounds to target ACE-2, spiked, protein, protease inhibitor. In Preliminary Studies and discussions with GVN: https://ostrovlab.pathology.ufl.edu/

Doherty Institute, Melbourne, Australia, Sharon Lewin and Damian Purcell

• Clinical work and sample collection. Studies in Pre-Clinical
• Drugs to establish IC50/Test repurposed drugs in-vitro, block receptor by spike

Target Protease inhibitor

• Hydroxychloroquine-lopinavir therapy

https://www.doherty.edu.au/news-events/news/covid-19-online-panel-discussion-held-at-the-doherty-institute

Florian Krammer-Mount Sinai, New York, NY

• Plasmapheresis-antibodies from recovered patients with COVID-19
• Collaborations: New York Blood Center and the New York State Department of Health’s Wadsworth Center laboratory in Albany and guidance from the U.S. Food and Drug Administration
• Challenge: identifying sufficient patients with antibodies; scale-up

Assay Development

• The assay is sensitive and specific, allowing for screening three days, post onset of symptoms.
• Use in plasmapheresis, the antibody test, using recombinant or manufactured antigens from the spike protein on the surface of the SARS-CoV-2.

https://inside.mountsinai.org/blog/mount-sinai-to-begin-the-transfer-of-covid-19-antibodies-into-critically-ill-patients/

University Queensland, David Paterson

• Chloroquine & lopinavir/ritonavir. Studies in Pre-clinical
• 45 Patients Trial, awaiting more people for clinical trials by month’s end

https://www.uq.edu.au/news/article/2020/03/researchers-set-begin-clinical-trials-potential-coronavirus-treatment

IRTA-CReSA Institute of Agrifood Research and Technology and Department of Animal Health, Barcelona, Spain, Natalia Majo

• MERS-CoV strains from 3 different clades (A, B and C). Studies in Preliminary/Animal Models
• Reagents: samples from MERS-CoV-experimentally infected lamas/alpacas/dromedary camels/pigs (sera, nasal swabs, tissues)
• nCoV, SARS viruses and other reagents currently available.
• Sera, nasal swabs, tissues assays; also, in vitro/in vivo animal model vaccines and antivirals
• Sera from vaccinated dromedaries and llamas, and also from MERS-CoV positive control animals, assess the cross-reactivity against SARS-CoV and nCoV

http://www.irta.cat/en/natalia-majo-fighting-against-the-diseases-of-the-future-will-be-harder-if-there-is-no-more-investment-in-animal-health/

AIDRC, St. Lucia, Queensland, Australia, Alexander Khromykh  

• Fixed cell ELISA test using cells either infected with SARS-CoV-2 or cell stability expressing spike protein from Kunjin virus replicon.
• Serum ferratin blood test
• Corticosteroid Therapy

KU Leuven Riga Institute, Leuven, Belgium, Johan Neyts

• PLLAV vaccine technology used for YF, LVD, Rabies and applied to nCovid-19; Goal-develop pan-corona virus dugs. Studies in Animal Models.
• Has isolates; Antiviral assays up and running lends good CPE
• Molecular libraries, (Gates) begin testing 20,000 molecules based on viral replication
• Next, Animal Models: mice & hamster lines; massive replication in the lungs
• Poses possible transmission vi+C36:C43a feces

https://search.kuleuven.be/en/Pages/results.aspx?k=#k=covid-19%20and%20johan%20neyts

Lawrence Blatt, Global Head of Infectious Diseases, Janssen Pharmaceuticals, President and CEO Alios Biopharma, GVN Board Member, South San Francisco

• Alpha Interferon with fewer side-effects and corticosteroids. In Clinical trials
• Protease inhibitor experimentations
• Hand-held diagnostics device

See Other Immunomodulators/interferon and Blatt, L.:

https://www.elsevier.com/__data/assets/pdf_file/0007/988648/COVID-19-Drug-Therapy_Mar-2020.pdf

Raymond Schinazi, Director Laboratory Biochemistry and Pharmaceuticals, Emory University , Atlanta, Georgia

• Has the isolates
• Testing 5 Compounds affecting immunity and inflammation, use with nucleotide affect receptor, identify protease Inhibitors; scaling-up.
• Animal models-Remdesivir and anti-inflammatory in human studies with the VA.

https://www.nature.com/articles/s41422-020-0282-0

Wyss Institute at Harvard, Donald Ingber

• Engineered, SARS-CoV-2 pseudovirus. Collaborating with GVN (Number Centers/PIs)
• Covid-19 Human Lung Chip Model. Set-up Chip model in GVN Centers with technology purchase from Ingber’s company: emulate.bio.com. Proposes with BSL-4. Pseudovirus to study-capture agent FcMBL binds to Covid-19, efficiently; various other therapeutics. Testing to detect infection and viral entry-Airway Chips.
• Inhibition of viral entry (measured in this pseudovirus system) in Airway Chips, using multiple known and novel agents, including multiple FDA approved drugs were detected.
• Collaborate, Matthew Frieman, University of Maryland: installing Organ Chip instruments on his site, testing identified drugs and FcMBL capture technology.

https://wyss.harvard.edu/news/news-the-wyss-institutes-response-to-covid-19-beating-back-the-coronavirus/

NIAID, Bethesda, Maryland and Rocky Mountain Labs

• Studies in Animal Models-Vaccine candidate-chimp adenovirus-vector
• Remdesivir and Lopinavir/ritovinir studies

Implications of antibody-dependent enhancement of infection for SARS-CoV-2 countermeasures
Nature, June 5, 2020 

Classical drug digitoxin inhibits influenza cytokine storm, with implications for COVID-19 therapy
BioRxiv, April 13, 2020 

Antibody Points to Possible Weak Spot on Novel Coronavirus
NIH Director’s Blog, April 14, 2020 

Compassionate Use of Remdesivir for Patients with Severe Covid-19
NEJM, April 10, 2020

Crystal structure of SARS-CoV-2 main protease provides a basis for design of improved α-ketoamide inhibitors
Science, March 20, 2020

Soluble angiotensin-converting enzyme 2: a potential approach for coronavirus infection therapy?
Portland Press, March 13, 2020

Drugs are possibly effective for 2019-nCoV include: remdesivir, lopinavir/ritonavir, lopinavir/ritonavir combined with interferon-β, convalescent plasma, and monoclonal antibodies
NCBI, March 12, 2020

Potential benefits of precise corticosteroids therapy for severe 2019-nCoV pneumonia
NCBI, February 21, 2020

Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro
Nature, February 4, 2020