Other SARS-CoV-2 Updates – Therapeutics

SARS-CoV-2 Updates – Therapeutics

Other SARS-CoV-2 updates

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

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

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.

https://www.trialsitenews.com/fujifilm-toyama-chemicals-favipiravir-shows-some-promise-in-japanese-and-chinese-covid-19-clinical-trials/

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

https://newsroom.regeneron.com/news-releases/news-release-details/regeneron-and-sanofi-begin-global-kevzarar-sarilumab-clinical

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

https://www.takeda.com/newsroom/newsreleases/2020/takeda-initiates-development-of-a-plasma-derived-therapy-for-covid-19/

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

https://www.precisionvaccinations.com/vaxil-bio-covid19-vaccine-candidate-based-patent-protected-signal-peptide-technology

For a more complete listing of PhARMA/Biotech COVID-19 Treatment and Therapy:

https://www.clinicaltrialsarena.com/analysis/coronavirus-mers-cov-drugs/