# GS-441524 is Pharmacodynamically Equivalent to Remdesivir and Pharmacokinetically Superior Drug for the Treatment of COVID-19

> **NIH NIH R21** · UNIVERSITY OF TX MD ANDERSON CAN CTR · 2021 · $442,002

## Abstract

ABSTRACT. Covid-19 is a once in a generation epidemic that has had dire, destabilizing impacts across the
world. While remdesivir has emerged as the only drug with proven efficacy, its widespread distribution has been
plagued by supply-shortages. Careful review of pre-clinical data evidence that these problems largely derive
from the poorly optimized phosphate pro-drug moieties on remdesivir, which ultimately make manufacturing
remdesivir more difficult. Careful review of the literature indicates that, its parent nucleoside, GS-441524, is likely
the more optimal Covid-19 drug. We hypothesize that GS-441524 is pharmacodynamically equivalent drug to
remdesivir, in its ability to generate active nucleotide triphosphate to inhibit the SARS-CoV-2 RNA polymerase.
In addition to GS-441524 being significantly easier to synthesize, we contend that its direct administration would
enable homogenous tissue distribution of active nucleotide triphosphate inhibitor compared to remdesivir; higher
levels of inhibitor would ultimately be achieved in lung epithelial cells most afflicted by SARS-CoV-2.
This proposal will make fundamental biochemical advances at the in vitro level and therapeutic advancements
at the in vivo level. We will compare the rates bioactivation of GS-4441524 and remdesivir across a broad panel
of primary human cell types and delineate the exact molecular mechanism and enzymes which bio-transform
remdesivir and GS-441524 into the active triphosphate species. At the same time, we will establish
pharmacodynamic equivalence between GS-441524 and remdesivir in mice and non-human primates. Finally,
we will demonstrate that GS-441524 is ultimately superior to remdesivir in vivo for generating active triphosphate
inhibitor, when each is administered at their maximum tolerated doses. Should our hypotheses prove correct,
these data will support GS-441524 for IND and clinical trials.

## Key facts

- **NIH application ID:** 10199288
- **Project number:** 1R21AI159246-01
- **Recipient organization:** UNIVERSITY OF TX MD ANDERSON CAN CTR
- **Principal Investigator:** CHUN LI
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $442,002
- **Award type:** 1
- **Project period:** 2021-01-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10199288

## Citation

> US National Institutes of Health, RePORTER application 10199288, GS-441524 is Pharmacodynamically Equivalent to Remdesivir and Pharmacokinetically Superior Drug for the Treatment of COVID-19 (1R21AI159246-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10199288. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*