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Principal Investigator: Scott F Michael
Organization: COLLEGE AT OSWEGO
Fiscal Year: 2022
Award: $155,018
Funding agency: National Institute of General Medical Sciences
PROJECT SUMMERY
Most currently available vaccines, especially live and mRNA-based COVID-19 vaccines, are temperature sensi-
tive and require stringent cold-chain maintenance, entailing their storage and distribution at recommended tem-
peratures from production to administration. This necessity imposes the most prohibitive barrier to global im-
munization programs, particularly in developing countries, accounting for up to 80% of the cost delivery. Thus,
there is a critical need for a technology to provide cost-effective and long-term ambient temperature storage for
viral samples without requiring cold chain or complicated sample recovery protocols.
This proposal aims to develop an organic-ion platform for long-term storage of viruses at ambient tem-
perature to potentially reduce costs in the face of growing needs for new vaccines and avoid labor-intensive
maintenance associated with current biobanking technology. Ionic liquids (ILs) organic salts comprised entirely
of ions offer a well-suited platform on which the properties can be altered by the selection of ions, enabling the
tunable design of solvents/media for virus stabilization. We hypothesize that the solutions of proposed ILs with
ca. 20 wt% water may prevent hydrolytic and enzymatic degradation of viral genomes and protein capsids,
providing a reliable approach to preserve viruses. We will use a bacteriophage from the myovirus family as an
example of a naked protein particle and dengue virus as an example of a lipid-enveloped particle. First, we will
develop a thoughtfully conceived library of novel ILs through systematic variations of heterocyclic cations and
kosmotropic anions, and judicious incorporation of two functionalities (NH3+ and SO2F) into the IL structures.
Structural variability will be achieved by pairing new genre of biocompatible cations and anions. Second, we will
examine their effectiveness for stabilizing viruses by evaluating their structural integrity, thermostability, and
shelf-life from six months and four year. We will monitor changes in viral secondary structure, thermal denatur-
ation, and particle morphology. Last, we will study their empirical structure-activity relationships to gain compre-
hensive understanding of binding characteristics and molecular mechanisms of interactions between the viral
particles and the targeted aqueous ionic solvents via simulation, crystallographic, and spectroscopic methods.
This project will provide a viable solution for ambient temperature preservation of viruses for extended
periods (potentially for decades) by developing the virusILwater matrices that are stable towards hydrolytic
and enzymatic degradation. Another important feature of the proposed approach is that these nucleic acid-ILs
solutions can be directly amplified by PCR without being subjected to prior extraction, purification or quantifica-
tion. This approach has the merit of simplicity, which makes the process of ambient temperature storage and
distribution profoundly efficient, increases the stability of biosamples for prolonged time, reduces operational
costs and carbon footprint, and improves logistics for viruses and virus-based technologies.
Summery
Terms: <2019-nCoV vaccine><Accounting><Acids><Affect><Ammonium><Anions><Assay><Bacteriophages><Base Pairing><Benign><Binding><Bioassay><Biologic Assays><Biological Assay><Breakbone Fever Virus><Buffers><CD/ORD Spectroscopy><COVID-19><COVID-19 vaccine><COVID19><COVID19 vaccine><CV-19><CV19><Calorimetric Differential Thermal Analysis><Capsid Proteins><Carbon><Cations><Characteristics><Circular Dichroism Spectroscopy><Coat Proteins><Cold Chains><Cryofixation><Cryopreservation><DNA><Dengue Virus><Dengue fever virus><Deoxyribonucleic Acid><Developing Countries><Developing Nations><Development><Differential Scanning Calorimetry><Effectiveness><Electrostatics><Enzyme Gene><Enzymes><Exhibits><Family><Fluorides><Formulation><Freezing><Future><Goals><H-bond><Hydration><Hydration status><Hydrogen Bonding><Hydrogen Oxide><Hydrolysis><Ions><Knowledge><Less-Developed Countries><Less-Developed Nations><Libraries><Life><Lipid Bilayers><Lipids><Liquid substance><Logistics><Low-resource area><Low-resource community><Low-resource environment><Low-resource region><Low-resource setting><Lytic><Lytotoxicity><Maintenance><Medicine><Messenger RNA><Methods><Mind><Modeling><Molecular><Molecular Interaction><Monitor><Morphology><Names><Nature><Nucleic Acid Vaccines><Nucleic Acids><Outcome><Phages><Polymerase Chain Reaction><Procedures><Process><Production><Property><Proteins><Protocol><Protocols documentation><QSAR><Quantitative Structure-Activity Relationship><Quantitiative Structure Activity Relationship><Recombinant Proteins><Recovery><Research Resources><Resource-constrained area><Resource-constrained community><Resource-constrained environment><Resource-constrained region><Resource-constrained setting><Resource-limited area><Resource-limited community><Resource-limited environment><Resource-limited region><Resource-limited setting><Resource-poor area><Resource-poor community><Resource-poor environment><Resource-poor region><Resource-poor setting><Resources><Reverse Transcription><Roentgen Rays><SARS-CoV-2 vaccine><SARS-CoV2 vaccine><SARS-coronavirus-2 vaccine><Salts><Sampling><Savings><Scanning><Scientist><Severe Acute Respiratory Syndrome CoV 2 vaccine><Severe acute respiratory syndrome coronavirus 2 vaccine><Solvents><Structure><Structure-Activity Relationship><Techniques><Technology><Temperature><Third-World Countries><Third-World Nations><Time><Toxicology><Transmission Electron Microscopy><Transportation><Under-Developed Countries><Under-Developed Nations><Vaccination><Vaccines><Variant><Variation><Viral><Viral Coat Proteins><Viral Gene Products><Viral Gene Proteins><Viral Genome><Viral Outer Coat Protein><Viral Proteins><Virus><Virus-like particle><Water><X-Radiation><X-Ray Radiation><X-ray><Xray><access to vaccination><access to vaccines><aqueous><bacterial virus><base><biobank><biocompatibility><biomaterial compatibility><biorepository><chemical structure function><cold preservation><cold storage><corona virus disease 2019><corona virus disease 2019 vaccine><coronavirus disease 2019><coronavirus disease 2019 vaccine><coronavirus disease-19><coronavirus disease-19 vaccine><coronavirus infectious disease-19><cost><cost effective><cytotoxicity><deploy vaccines><design><designing><developing country><developing nation><developmental><distribute vaccines><fighting><flu><fluid><functional group><global health><improved><light scattering><lipid bilayer membrane><liquid><liquid formulation><mRNA><neglect><new vaccines><next generation vaccines><novel><novel vaccines><nucleic acid stability><nucleic acid-based vaccine><outcome following vaccination><outcome following vaccine><pandemic><pandemic disease><particle><preservation><prevent><preventing><programs><rational design><result following vaccination><result following vaccine><simulation><solute><stressor><structure function relationship><tech development><technology development><thermolability><thermostability><vaccination access><vaccination availability><vaccination outcome><vaccination result><vaccine access><vaccine against 2019-nCov><vaccine against SARS-CoV-2><vaccine against SARS-CoV2><vaccine against SARS-coronavirus-2><vaccine against Severe Acute Respiratory Syndrome CoV 2><vaccine against Severe acute respiratory syndrome coronavirus 2><vaccine availability><vaccine deployment><vaccine distribution><vaccine for novel coronavirus><vaccine outcome><vaccine result><vaccine roll-out><vaccine rollout><virus genome><virus protein><virus-like nanoparticles><viruslike particle><water diffusion>