AI-Enabled Discovery of Broad-Spectrum Small-Molecule Inhibitors for Filoviruses

AI-Enabled Discovery of Broad-Spectrum Small-Molecule Inhibitors for Filoviruses Purpose: The purpose of this Request for Information (RFI) is to conduct market research to identify organizations with capabilities in artificial intelligence (AI) for application in the discovery and advancement of broad-spectrum, small-molecule therapeutics targeting filoviruses (e.g., Ebola virus (EBOV), Sudan virus (SUDV), Marburg virus (MARV)). This RFI seeks information on technical capabilities, infrastructure, prior experience, and recommended approaches. Areas of interest include: AI-driven design, in vitro verification of hits, and early preclinical proof-of-concept evaluation. Information obtained through this RFI will inform acquisition planning and may shape the scope and structure of a future solicitation. Respondents may propose teaming arrangements or partnerships to address the full scope of capabilities described in this RFI. Request for Information Respondents do not have to be a member of the RRPV consortium to submit a response for this RFI; however, they must be a member of the consortium to respond to any future request for project proposals (RPP) for this requirement. Please submit responses by email to rrpv@ati.org no later than 1pm EDT June 17th, 2026 Late responses will not be considered. This RFI is for information gathering purposes only. It does not constitute a Request for Project Proposal (RPP) nor does it imply any obligation to issue a future solicitation, make any award, or pay any costs associated with responding to this RFI. Submission is voluntary and does not commit the responder to respond to any subsequent opportunities (if any) related to this topic. The RRPV will not return or provide feedback on any submissions, however, BARDA reserves the right to further engage with respondents in a Market Research Call to clarify understanding of submitted information. All responses to this RFI will be treated as sensitive information and confidentiality will be protected accordingly. Background: Filoviruses are high-consequence pathogens requiring BSL-4 containment and represent ongoing biodefense and global health threats. The current small-molecule antiviral pipeline remains limited, and no small-molecule therapeutics have been approved for treatment of filovirus infection. Advances in AI, structure-based modeling, molecular dynamics, and computational chemistry provide opportunities to modernize antiviral discovery and enable the identification of small-molecule therapeutics that target conserved viral functions critical to filovirus replication and pathogenesis. Technical Focus: The potential funding effort is expected to span AI-enabled discovery through lead selection and preclinical in vitro and in vivo testing in small animal models. Preference is for direct-acting antiviral treatment approaches; however, host-targeted approaches relevant to viral replication may also be considered. Approaches targeting host dysregulation or disease state are out of scope, as are nucleic acid-based therapeutics and candidates being developed for a prophylactic indication. Broad-spectrum activity across EBOV, SUDV, and MARV will be required, with preference for candidates also demonstrating efficacy against other negative-sense RNA viruses. Through this RFI, BARDA seeks input on approaches to discover and advance potent, safe, broad-spectrum, small-molecule therapeutics targeting filoviruses using advanced analytics, including AI-enabled and other in silico methods. Specific Questions for Respondents: Respondents are requested to address BARDA’s interest in the discovery and advancement of potent, safe, broad spectrum, small molecule inhibitors of filoviruses. A. Strategic Scope 1) What are the risks and benefits of releasing a potential future funding initiative focused on a specific viral target (e.g., a defined protein or stage of the viral life cycle) as opposed to a broader approach for anti-filovirus activity without a prescribed target? Describe how your approach would differ under each scenario (target-specific vs. virus family–level development). 2) Nucleoside analog RNA-dependent RNA polymerase (RdRp) inhibitors have demonstrated effective antiviral activity against filoviruses but have faced limitations in safety/toxicity, pharmacokinetics, and/or potency. a. How could your approach improve upon this specific class of compounds for filoviruses? b. What are the key benefits and risks/challenges of a program focused on nucleoside/nucleotide analogs for filoviruses? Provide concise technical rationale addressing risk, feasibility, timelines, and expected impact. B. Technical Capabilities 3) BARDA is considering a funding initiative focused on small molecule therapeutics targeting filoviruses, which could include novel chemical structures, peptides, and other synthetic molecules. a. What types of small molecule modalities does your organization produce? Describe the benefits an