# Technology Opportunity: Accelerating the Development of Orally Bioavailable Therapeutics for Beta-Coronaviruses with Structure-Based Molecular Design Canonical: https://abierto.us/opportunities/9fa332bd07e94b8cb429911b9a9130a2 - Notice type: Special notice - Status: Closed. Deadline was December 1, 2023 at 5:00 PM EST - Department: Department of Energy - Contracting office: ORNL Ut-Battelle LLC-DOE Contractor (899042) - Place of performance: Oak Ridge, Tennessee - County: Anderson County (FIPS 47001). https://abierto.us/counties/anderson-county-tn-47001 - City: Oak Ridge. https://abierto.us/cities/oak-ridge-tn-4755120 - First posted: February 13, 2024 - Last posted: February 13, 2024 - SAM.gov: https://sam.gov/workspace/contract/opp/9fa332bd07e94b8cb429911b9a9130a2/view ## Description Oak Ridge National Laboratory (ORNL) is seeking a commercialization partner for a technical business opportunity entitled Accelerating the Development of Orally Bioavailable Therapeutics for Beta-Coronaviruses with Structure-based Molecular Design. There is a critical need for new antiviral drugs for treating infections of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). New drugs are crucial for rapid therapeutic response to COVID-19, supporting ongoing vaccination campaigns and expanding future antiviral drug options. SARS-CoV-2 variants can evade vaccines and antibody treatments; new variants continue to emerge and are expected to cause future outbreaks. The problem is relevant to national and global public health and is specifically important to economic stability and national security. Solution Through rational and computational design, an ORNL team developed a potent and selective covalent inhibitor of the papain-like protease (PLpro) of SARS-CoV-2. PLpro is a critical target because it is essential for viral proliferation and dysregulates the host immune response. The team’s best lead to date has a half-maximal inhibitory concentration of 38 nM and half-maximal effective concentration in multiple SARS-CoV-2 variants ranging from 0.32–1.3 µM in vitro. However, in vivo efficacy is limited by rapid metabolic degradation. The team aims to improve the metabolic stability and oral bioavailability by designing new compounds based on our current best leads. Impact A successful therapeutic could capture a significant percentage of the total coronavirus current and future therapy market. Investments from domestic and international governments for preparedness stocks for future novel coronavirus outbreaks offer potential revenue. There has been a significant loss of life due to SARS-CoV-2 infections over the last three years, upwards of 6.8 million lives lost. Accordingly, there is a desperate need for new antiviral drugs that would have an enormous societal benefit on global health, security, and economics. Publications Sanders, B. C.; Pokhrel, S.; Labbe, A. D.; Mathews, I. I.; Cooper, C. J.; Davidson, R. B.; Phillips, G.; Weiss, K. L.; Zhang, Q.; O’Neill, H…. Parks, J.M. Potent and selective covalent inhibition of the papain-like protease from SARS-CoV-2. Nat. Commun. 2023, 14 (1), 1733. Intellectual Property Invention Ref. No. 202004743. US Patent Applic. No. 17/896,182 entitled “Covalent Inhibitors of Coronavirus Papain-Like Protease” filed on August 26, 2022; PCT Patent Applic. No. US2022/041629 filed on August 26, 2022. About Oak Ridge National Laboratory and the Technology Innovation Program Oak Ridge National Laboratory is helping to speed new technologies to market while also building supportive and resilient ecosystems to the benefit of our local, state, and national communities. The depth and breadth of our wide-ranging, world-leading expertise and facilities are unparalleled and provide a competitive advantage to our partners. The Technology Transfer team is driven by a shared mission to connect the lab’s unique strengths in scientific discovery, clean energy technology, and national security to the world’s biggest challenges. ORNL’s Technology Innovation Program accelerates commercial adoption of promising lab-developed technologies by making targeted investments that enhance commercial readiness and raise a technology’s visibility in the region. Since 2012, ORNL has invested more than $11 million in 49 projects, resulting in 37 commercial licenses and options with partners ranging from Fortune 100 companies to early-stage startups. ## Publications - February 13, 2024: Special notice, due December 1, 2023 at 5:00 PM EST. Notice 9fa332bd07e94b8cb429911b9a9130a2. https://sam.gov/workspace/contract/opp/9fa332bd07e94b8cb429911b9a9130a2/view ## Points of contact - Alex DeTrana, detranaag@ornl.gov, 8653410423 --- Source: SAM.gov Contract Opportunities bulk extract. Confirm deadlines on SAM.gov before responding. Cite https://abierto.us/opportunities/9fa332bd07e94b8cb429911b9a9130a2.