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Principal Investigator: Stacy Remiszewski
Organization: EVRYS BIO, LLC
Fiscal Year: 2020
Award: $901,086
Funding agency: National Institute of Allergy and Infectious Diseases
In response to the Notice of Special Interest regarding the Availability of Emergency Competitive Revisions for
research on SARS-CoV-2 and COVID-19 (NOT-AI-20-034), the proposal herein is focused on the development
of SARS-CoV-2 therapeutic candidates with broad-spectrum activity against multiple coronavirus strains. It is
submitted as an Emergency Competitive Revision (PA-20-135) to an existing NIAID SBIR Phase II award titled
“A single antiviral to treat multiple opportunistic infections” (R44AI114079). The existing Phase II award is based
on the discovery that human sirtuin-2 protein (SIRT2) modulates the replication and spread of many different
viruses. The applicant, Evrys Bio, LLC, has developed a lead series of >550 SIRT2 inhibitors that exhibit broad-
spectrum antiviral activity. Excellent progress for the existing award has been made in the identification of a
Development Candidate ready for IND-enablement (DC). The candidates for DC selection show broad-spectrum
activity against human cytomegalovirus (HCMV) and other opportunistic agents causing disease in
immunosuppressed transplant patients. Indeed, Evrys SIRT2 inhibitors block the growth of many different
viruses in addition to HCMV, including DNA viruses (Epstein-Barr virus, BK virus, Hepatitis B virus) and RNA
viruses (influenza A and B, respiratory syncytial virus, Zika virus, Junin virus, Marburg virus and coronaviruses).
Of special relevance to this application, an Evrys SIRT2 inhibitor was shown to inhibit the production of progeny
by the human alpha-coronavirus HCoV-229E (EC50 = 1.6 µM) and beta-coronavirus HCoV-OC43 (EC50 = 0.54
µM). OC43 was studied in greater detail, and production of its N and M RNA as well as N protein were
dramatically inhibited in human MRC-5 cells. This proposal leverages the funding and progress of the existing
SBIR Phase II award to identify and advance a Development Candidate with broad-spectrum antiviral activity.
Proposed competitive revision Specific Aims focus on development of SARS-CoV-2 aspects of the broad-
spectrum therapeutic: SARS-CoV-2 activity will be tested to select the DC from among nine SIRT2 inhibitors
(active against beta-coronavirus OC43) already satisfying Target Compound Profile criteria for development
including broad-spectrum antiviral effectiveness and suitability for pharmaceutical development. To speed a
therapeutic solution to patients in need, the selected broad-spectrum DC (including SARS-CoV-2 antiviral
activity) will be advanced through IND enabling studies. In parallel, a back-up DC will be obtained. Evrys has
extensively characterized the lead series with respect to quantitative structure activity relationships (QSAR)
predicting HCMV antiviral activity and allowing for optimization of pharmaceutical properties. The algorithms
will be retrained for coronavirus to select a back-up optimized for coronavirus potency and pharmaceutical
properties (e.g., good lung distribution) for treatment of COVID-19. Extension of the parent grant's original aims
is possible because Evrys' well-characterized SIRT2 inhibitor series exhibits broad-spectrum antiviral activity,
including anti-coronavirus activity.
Terms: <2019 novel coronavirus><2019-nCoV><Address><Algorithms><Animal Model><Animal Models and Related Studies><Antiviral Agents><Antiviral Drugs><Antivirals><Argentine hemorrhagic fever virus><Argentinian Hemorrhagic Fever Virus><Award><BK Polyomavirus><BK Virus><BKV virus><Back><Bioavailability><Biologic Availability><Biological Availability><Burkitt Herpesvirus><Burkitt Lymphoma Virus><CMV><COVID-19><COVID-19 epidemic><COVID-19 pandemic><COVID19><COVID19 epidemic><COVID19 pandemic><Cell Body><Cells><Clinical><Communicable Diseases><Coronaviridae><Coronavirus><Cytomegalovirus><DMSO><DNA Viruses><Data><Demasorb><Demeso><Development><Dimethyl Sulfoxide><Dimethylsulphinyl><Dimethylsulphoxide><Disease><Disorder><Domoso><Dorsum><Dose><Dromisol><Drug Controls><Drug resistance><Drugs><E-B Virus><EB virus><EBV><Effectiveness><Emergencies><Emergency Situation><Enrollment><Enzyme Gene><Enzymes><Epstein Barr Virus><Exhibits><Formulation><Frankfurt-Marburg Syndrome Virus><Funding><Future><Generalized Growth><Genes><Growth><HBV><HCMV><HCoV><HHV 5><HHV-4><HHV4><HHV5><Harvest><Hepatitis B Virus><Homologous Serum Hepatitis Virus><Human><Human Herpesvirus 4><Human Herpesvirus 5><Immunity><In Vitro><Incubated><Infection><Infectious Disease Pathway><Infectious Diseases><Infectious Disorder><Infectious Mononucleosis Virus><Influenza A><Influenza A virus><Influenza B><Influenza B Virus><Influenza Viruses Type A><Influenza Viruses Type B><Influenzavirus A><Junin><Junin virus><Knowledge><Lead><London><Lung><Lung Respiratory System><Marburg><Marburg virus><Medication><Modern Man><NIAID><National Institute of Allergy and Infectious Disease><Non-Polyadenylated RNA><Opportunistic Infections><Oral><Orthomyxovirus Type A><Orthomyxoviruses Type B><Parents><Patients><Pb element><Pharmaceutic Preparations><Pharmaceutical Agent><Pharmaceutical Preparations><Pharmaceuticals><Pharmacologic Substance><Pharmacological Substance><Phase><Physiologic Availability><Production><Property><Proteins><QSAR><Quantitative Structure-Activity Relationship><Quantitiative Structure Activity Relationship><RNA><RNA Gene Products><RNA Viruses><Reporting><Research><Respiratory syncytial virus><Ribonucleic Acid><SARS-CoV-2><SARS-CoV2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-related coronavirus 2><SBIR><Salivary Gland Viruses><Series><Severe acute respiratory syndrome coronavirus 2><Silent Mating Type Information Regulator 2-like Proteins><Sir2-like Proteins><Sirtuins><Small Business Innovation Research><Small Business Innovation Research Grant><Speed><System><Testing><Therapeutic><Tissue Growth><Transcript><Transplant Recipients><Transplantation><Type A Influenza><Viral><Viral Diseases><Virus><Virus Diseases><Virus Replication><Western Blotting><Western Immunoblotting><Wuhan coronavirus><ZIKV><Zika Virus><anti-viral agents><anti-viral drugs><anti-virals><base><beta Actin><candidate selection><college><collegiate><corona virus><corona virus disease 2019><corona virus disease 2019 epidemic><corona virus disease 2019 pandemic><coronavirus disease 2019><coronavirus disease 2019 epidemic><coronavirus disease 2019 pandemic><cytomegalovirus group><develop a vaccine><development of a vaccine><developmental><drug resistant><drug/agent><enroll><heavy metal Pb><heavy metal lead><human CoV><human corona virus><human coronavirus><immunosuppressed><inhibitor><inhibitor/antagonist><interest><lead optimization><lead series><man><man's><meetings><model of animal><model organism><new approaches><new drug target><new druggable target><new pharmacotherapy target><new therapeutic target><new therapy target><novel approaches><novel drug target><novel druggable target><novel pharmacotherapy target><novel strategies><novel strategy><novel therapeutic target><novel therapy target><ontogeny><pandemic><pandemic disease><parent grant><protein B><protein blotting><pulmonary><resistance to Drug><resistant to Drug><response><standard of care><therapeutic candidate><transplant><transplant patient><vaccine development><vaccine formulation><viral infection><viral multiplication><viral replication><virus infection><virus multiplication><virus-induced disease><zikav><β-Actin>