The First LANCL2-based therapeutic for influenza Biotherapeutics, Inc (BTI) is a clinical-stage biotech company that synergistically combines the power of advanced computational modeling with translational experimentation to accelerate the development of novel products for precision medicine and health. This Phase 1 SBIR application emerges from substantial preclinical data showing the potential of lanthionine synthetase C-like 2 (LANCL2) agonists as host-based therapeutics for viral diseases. Our Product: BT-63, a novel lead LANCL2 agonist ligand, selectively binds to LANCL2 and exerts promising therapeutic efficacy in mouse models of influenza A virus (IAV). In this Phase I we will focus on influenza virus to characterize the role of LANCL2 as therapeutic target with broad antiviral effects. Background: infectious diseases caused by emerging and re-emerging viruses are a significant public health challenge. Influenza remains a significant public health threat despite available antivirals and vaccines. The absence of effective universal vaccines and antivirals coupled with the rising rates of antiviral resistance justifies the need to develop novel host-based antivirals. BTI identified LANCL2 as a novel target during viral infections. LANCL2 agonistic drugs down-regulate viral entry and replication while protecting against the virus-induced cytokine storm, mortality, pathology and disease. The Specific Aims of this SBIR Phase 1 application are to: AIM 1. Validate LANCL2 as a new host target for treating influenza infections: we will to optimize dosing and therapeutic window and validate LANCL2 as the molecular target of BT-63. AIM 2: Evaluate the antiviral mechanisms and spectrum of BT-63: we will test the hypothesis that BT-63 exerts broad spectrum antiviral effect by modulating metabolic responses of the host cell. Mayor expected outcomes: BT-63 offers at least a 50% protection against mortality, suppresses by 10-fold the expression of proinflammatory markers IL-6 and TNFα, the mechanism is LANCL2-dependent, and BT-63 has broad antiviral spectrum against pH-dependent viruses. . SBIR Phase II will assess the potential for synergism with and comparison against current antivirals and vaccines, expand LANCL2 efficacy and antiviral knowledge into other viruses and advance lead derivatives along the FDA regulatory pathway through ADME-Tox and safety assessments with a key milestone of submitting an IND application within 1 year of funding. Commercial Application: Technology generated by this R&D project could disrupt a $50B annual market.