# Development and validation of antivirals against hemorrhagic fever viruses of pandemic concern

> **NIH NIH U19** · SCRIPPS RESEARCH INSTITUTE, THE · 2022 · $2,257,057

## Abstract

SUMMARY
Lassa virus (LASV), severe fever with thrombocytopenia syndrome virus (SFTSV), and Ebola virus (EBOV)
are hemorrhagic fever causing viruses (HFV) of pandemic concern that pose a threat to public health, a
situation exacerbated by an overall lack of effective antiviral therapeutics to combat these infections. Despite
their different genome organization and biology, mammarenaviruses (LASV), banyangviruses (SFTSV) and
filoviruses (EBOV) share a similar RNA biosynthetic strategy where the viral nucleoprotein encapsidates the
viral genome RNA to form a nucleocapsid (NC) that serves as template for RNA synthesis, both replication
and transcription, mediated by the associated viral RNA dependent RNA polymerase (RdRp, L protein) in the
context of a viral ribonucleoprotein complex (vRNP). The central goal of this Project 6 of CAMPP is to discover
and develop antivirals targeting viral components of LASV, SFTSV and EBOV vRNPs. For this, we have on
place cell-based and biochemical assays amenable to HTS to identify inhibitors of viral RdRp activity and NC
formation for LASV, SFTSV and EBOV, as well as the L protein endonuclease and cap-binding activities
required for LASV and SFTSV cap-snatching mediated transcription. Initial hits, identified by HTS using target-
specific cell based or biochemical assays, will be validated and, following target confirmation, subjected to a
common pipeline involving formal hit assessment (FHA), early and late hit-to-lead (H2L) steps, and lead
optimization (leadOP), which will facilitate IND-enabling steps outside the scope of this project. This research
project builds on the strong synergy with the CAMPP Cores. The Medicinal Chemistry and Structural and
Modeling Cores will use structure-based drug design to synthesize compound derivatives with improved
biological and pharmacokinetic properties, whereas the Animal Models of Infection Core will enable in vivo
efficacy studies of selected leads.

## Key facts

- **NIH application ID:** 10514329
- **Project number:** 1U19AI171443-01
- **Recipient organization:** SCRIPPS RESEARCH INSTITUTE, THE
- **Principal Investigator:** Juan C. de la Torre
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $2,257,057
- **Award type:** 1
- **Project period:** 2022-05-16 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10514329

## Citation

> US National Institutes of Health, RePORTER application 10514329, Development and validation of antivirals against hemorrhagic fever viruses of pandemic concern (1U19AI171443-01). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/10514329. Licensed CC0.

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