COVID-19 future or investigational therapies

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Future or Investigational Therapies

Anti-virals

• Chloroquine
• Arbidol
• Remdesivir
• Favipiravir

Vaccine

Immune Targets

• The B cell and T cell epitopes derived from the spike (S) and nucleocapsid (N) proteins are currently under investigation as immune targets for development of vaccine.
• Phylogenetic similarity between SARS-CoV and COVID-19 at the level of structural proteins S, E, M, and N is providing guidance for development of a possible vaccine.

Current Clinical Trials

The following countries are currently working on the development of a vaccine for COVID-19 (SARS-CoV2)

USA

• Beth Israel Deaconess Medical Center (BIDMC), Boston and Johnson & Johnson (J&J) are currently collaborating to advance COVID-19 vaccine. A Phase I trial is expected to launch during the last quarter of 2020. AdVac and PER.C6 technologies are being used for rapid production.
• National Institute for Allergy and Infectious Diseases (NIAID) has announced that a phase 1 trial has begun for COVID-19 immunization in Washington state.
• The trial includes 45 young, healthy volunteers with different doses of immunization shots co-developed by NIH and Moderna Inc.

Israel

• Researchers at Israel’s Institute for Biological Research are expected to announce in the coming days that they have completed development of a vaccine for COVID-19

China

• China was the first country to release the genetic sequence of the virus on open scientific databases so that research institutes and commercial companies could try to develop treatments and vaccines without needing to obtain samples.
• China has announced the first animal tests.

Australia

• Following successful in vitro experiments, animal testing has begun in University of Queensland in Australia

Prior Work

The following table depicts major vaccine products that have been developed against SARS-CoV and MERS-CoV:

Vaccine Base	Antigen	Clinical Testing	Pros	Cons
DNA	Spike protein S1	Phase I, II (NCT03721718)	Reduced production time Easy design and manipulation Stimulates B and T cells responses	Requires efficient intradermal gene gun delivery to antigen-presenting cells Weaker immune response compared to live vaccine
Viral Vector	Spike protein S1; Chimpanzee adenovirus vector, Modified Vaccinia Ankara	Phase I (NCT03399578, NCT03615911)	Competent immune response	Varied immune response based of mode of delivery Th2 bias
Conjugated subunit	Spike protein S1 Receptor binding domain Nucleocapsid Membrane protein Envelope protein Delta Inulin Adjuvant and/or fusion with Fc		Stimulates humoral and cellular responses Increased safety Ease of production	Reduced cost-effectiveness may hinder production Adjuvants required
Virion	Spike protein S1 Receptor binding domain Membrane protein Envelope protein Prepared in baculovirus		Multi-unit Preservation of whole virus	Requires optimum nucleocapsid assembly
Inactivated	Whole virus Formaldehyde or gamma irradiation inactivation		Preservation of whole virus Reduced production time Competent neutralizing antibody production Enhanced Protection while ameliorating lung eosinophilic immunopathology	Hypersensitivity reaction Th2-bias
Live attenuated	Mutant MERS-CoV and SARS-CoV or recombination with other live attenuated virus		Sensitivity to mutagenesis Excellent B and T cell response