# A single antiviral to treat multiple opportunistic infections

> **NIH NIH R44** · EVRYS BIO, LLC · 2020 · $901,086

## Abstract

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 p...

## Key facts

- **NIH application ID:** 10157407
- **Project number:** 3R44AI114079-03S1
- **Recipient organization:** EVRYS BIO, LLC
- **Principal Investigator:** Stacy Remiszewski
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $901,086
- **Award type:** 3
- **Project period:** 2020-08-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10157407

## Citation

> US National Institutes of Health, RePORTER application 10157407, A single antiviral to treat multiple opportunistic infections (3R44AI114079-03S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10157407. Licensed CC0.

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