# Teratogenicity assessment of new antiviral drugs using 3D morphogenesis models

> **NIH NIH R03** · UNIVERSITY OF HAWAII AT MANOA · 2023 · $156,500

## Abstract

Proposal Abstract
 Various drugs are known to be teratogenic, causing miscarriages or birth defects, when used during
pregnancy. However, teratogenicity is unclear for many other drugs, particularly those that were recently
marketed. Because of the ongoing COVID-19 pandemic/endemic, many investigators are developing new
antiviral drugs against SARS-CoV-2. Currently, three antivirals are approved or granted the emergency use
authorization by the FDA, namely remdesivir, molnupiravir, and Paxlovid. Yet studies on their teratogenicity are
scarce. As COVID-19 still persists with the emergence of immune escape variants, many people, including
those of childbearing potential, may require antiviral treatment. For physicians to provide proper advice for
their patients, the teratogenicity of the antivirals should be studied sufficiently. Previously, we invented the
mouse and human stem cell-based 3D morphogenesis models, which recapitulate the key features of early
embryogenesis in vitro and can serve as effective tools to sensitively and specifically detect various teratogenic
chemicals. Our Preliminary Studies using these morphogenesis models suggest that the anti-COVID-19
drugs, particularly remdesivir and molnupiravir, impair embryogenesis at the concentrations close to their
therapeutic plasma levels in human. These observations necessitate further investigations into the teratogenic
potential of the antivirals, as proposed in this application. Specifically, we will (1) characterize the molecular
impact of the new antivirals on the morphogenesis models, (2) explore the possible teratogenic mechanisms of
the new antivirals, and (3) examine the teratogenic effects of the new antivirals with the mouse whole embryo
culture. The proposed experiments should yield valuable information pertinent to their teratogenic potential,
such as the concentration-effect relationship and molecular mechanisms of actions, and help in the design and
interpretation of animal- and human-based studies in an effective manner.

## Key facts

- **NIH application ID:** 10741474
- **Project number:** 1R03HD110743-01A1
- **Recipient organization:** UNIVERSITY OF HAWAII AT MANOA
- **Principal Investigator:** YUSUKE MARIKAWA
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $156,500
- **Award type:** 1
- **Project period:** 2023-08-10 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10741474

## Citation

> US National Institutes of Health, RePORTER application 10741474, Teratogenicity assessment of new antiviral drugs using 3D morphogenesis models (1R03HD110743-01A1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10741474. Licensed CC0.

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