Other SARS-CoV-2 updates
Academia
GVN Centers
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
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.
University Queensland, David Paterson
- Chloroquine & lopinavir/ritonavir. Studies in Pre-clinical
- 45 Patients Trial, awaiting more people for clinical trials by month’s end
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
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.
Other Academic Updates
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
Industry
Gilead
- Remdesivir
- Collaborator-University of Nebraska Medical Center and China-Japan Friendship Hospital and Chinese Academy of Medical Sciences
- late-stage clinical trials, beginning in March
- Novel, nucleotide analog
- In Phase-2 with NIAID: adaptive, Random, Controlled Trial
- Phase-3: Safety & Efficacy will receive FDA’s rapid acceptance of Gilead’s IND filing
- Gilead is suspending access of Remdesimir due to overwhelming demand. Remdesivir was established for limited access. To stem demand, Gilead will pivot from accepting compassionate-use requests to only providing treatment through expanded access programs.
https://www.gilead.com/purpose/advancing-global-health/covid-19
Fujifilm Toyama Chemical Company
- Favipiravir/antiviral treatment
- Potent inhibitor of influenza, virus RNA polymerase. Broad spectrum of activity against many viral pathogens.
- Approved in China for manufacture.
Quercegen Pharma
- Clinical trials-invited to China to conduct trials
- Research collaborations with the Institute of Montreal
- Quercetin is safe, natural, flavonoid, plant-based, anti-inflammatory: Quercegen has obtained a GRAS (Generally Recognized as Safe) notice from FDA in 2010. Specific vaccines against Wuhan Coronavirus will not be ready for a few months. Quercetin shows antiviral activities against HCV, Human Respiratory Syncytial Virus, Influenza (H1N1, H5N1…), Ebola, Zika, Dengue, Enterovirus 71…Quercetin inhibits the viral enzyme 3C-like protease that is vital to Coronavirus replication. Readily Available, potent and active against Ebola and Zika. Meets safety regulations, therefore, may profile-skip animal testing; Affordability-cost-$2/day compared $1,000/day
https://www.drwalt.com/blog/2020/03/23/what-about-covid-19-and-quercetin/
Regeneron Pharmaceuticals
- REGN3048 and 3051
- HHS/BARDA
- Currently, in-vitro, but no access to clinical trials data
- Public/Private sectors; Hydroxychloroquine more tolerable, meets safety profile and more potent than Chloroquine. Neutralizing monoclonal antibodies. Fully human mAbs binding the spike protein of MERS-CoV. VelocImmune Platform, part of the company’s VelociSuite technology. Produced by a single clone of cells or a cell-line with identical antibody molecules. The antibodies bind to certain proteins of a virus, reducing the ability of the virus to infect human cells. In Phase-1 clinical trials.
Regeneron w/ Sanofi
- Produce-Sarilumab-mAB blocks IL-6 receptor
- Phase 2/3 clinical trials, beginning immediately, and will start to enroll patients
Takeda
- Blood Plasma-derived Therapy
- Need right concentration or IgG titers from recovered patients
- Pre-clinical testing and small-scale manufacturing; have robust, shared pre-clinical data with public and private sectors
- Assistance required to scale-up for USA and globally
Vaxil
- SARS-CoV-2 vaccine candidate based on a single peptide domains technology on key proteins for targeted therapy. VaxHit uses a Bioinformatics mAB Platform
- Vaxil’s mAb platform directly recognizes the target protein expressed on malignant cells and recruits other elements of the immune system to lyse those cells.
- Phase-1 Approved by the FDA and Euro Medical Agencies
For a more complete listing of PhARMA/Biotech COVID-19 Treatment and Therapy:
https://www.clinicaltrialsarena.com/analysis/coronavirus-mers-cov-drugs/