Halicin: A Dual-Action Molecule Against COVID-19 – New Findings from AVITHRAPID
AVITHRAPID scientists uncover how a repurposed antibiotic disrupts the core of the coronavirus replication machinery – opening new doors for broad-spectrum antiviral development. A Strategic Target: The Viral Protease 3CLpro SARS-CoV-2, the virus behind COVID-19, uses a specific enzyme, the 3C-like protease (3CLpro), to process its polyproteins. After infecting a cell, the virus synthesizes large protein chains that must be cut into smaller, functional pieces. This cutting task is performed by 3CLpro, a molecular scissor that is absolutely essential for viral replication. Without this function, the virus cannot reproduce. This makes 3CLpro one of the most promising targets for antiviral drugs. Medicines like Paxlovid work by inhibiting this enzyme, preventing the virus from completing its replication cycle. What makes 3CLpro even more interesting is that it is highly conserved among coronaviruses, meaning that drugs targeting this enzyme could be effective not only against SARS-CoV-2, but also other existing and future coronaviruses. Halicin: A Drug with Many Lives Halicin is not a traditional antiviral. In fact, it was first studied as a treatment for diabetes but failed in clinical development. Years later, it was rediscovered through artificial intelligence as a powerful antibiotic capable of killing multi-drug-resistant bacteria. Halicin works in a novel way by disrupting how bacteria maintain internal energy balance. Because of this, it bypasses many traditional resistance mechanisms. But halicin’s story didn’t stop there. Its unique chemical structure, particularly its reactivity with cysteine residues, has now attracted the attention of antiviral researchers. Could halicin, originally an AI-discovered antibiotic, also inhibit viral proteins? AVITHRAPID’s Discovery: Dual Binding to 3CLpro In a recent study published in the International Journal of Biological Macromolecules, AVITHRAPID scientists investigated halicin’s effect on the SARS-CoV-2 3CLpro enzyme. What they found was surprising and highly promising: halicin binds not just to the enzyme’s catalytic site, but also to a second, previously underappreciated site. Mass spectrometry and crystallography showed that halicin covalently attaches to Cys145, the critical residue in the enzyme’s active site. This kind of binding directly blocks the protease’s ability to process viral proteins. But more interestingly, halicin also binds to another cysteine: Cys44. To test how important Cys44 is, the researchers created a mutant version of 3CLpro, replacing Cys44 with alanine. The results were clear. This mutation significantly weakened the enzyme’s stability and reduced its ability to function. Further thermal stability assays confirmed that removing or modifying Cys44 disrupts the structural integrity of the entire protease. This means halicin is working in two ways: it directly inhibits the protease’s cutting function and simultaneously destabilizes the enzyme’s structure. It’s a dual-action mechanism that could make drug resistance more difficult and inhibition more effective. Implications for Future Antiviral Strategies The AVITHRAPID findings suggest that halicin – and potentially other molecules with similar reactivity – could be developed into broad-spectrum antivirals. By targeting multiple sites on a viral enzyme, especially those important for structure and function, drugs can become more robust and less vulnerable to resistance mutations. Importantly, halicin was not designed to be an antiviral. Its discovery as a 3CLpro inhibitor underscores the value of drug repurposing – one of the core goals of the AVITHRAPID initiative. Identifying hidden potential in known compounds can dramatically shorten development timelines in a health emergency. In addition, since 3CLpro is highly conserved across coronaviruses, halicin-like inhibitors may provide protection against future coronavirus outbreaks, making them valuable tools for pandemic preparedness. AVITHRAPID’s Role in Accelerating Antiviral Innovation AVITHRAPID is a European project dedicated to discovering and advancing broad-spectrum antiviral candidates through smart repurposing and high-throughput technologies. The halicin study exemplifies this mission by showing how computational prediction, structural biology, and biochemical testing can come together to reveal new therapeutic strategies. By exploring molecules that affect multiple viral mechanisms simultaneously, AVITHRAPID contributes not just to fighting current diseases, but to building resilience against future viral threats. The identification of Cys44 as a novel vulnerability in the viral protease adds a valuable new piece to the antiviral research puzzle. Conclusion Halicin’s dual targeting of 3CLpro represents a breakthrough in understanding how repurposed drugs can be used to combat viruses in ways not previously imagined. The research by AVITHRAPID scientists not only validates the approach of multi-target inhibition, but also brings attention to new structural weak points in the viral machinery. In a world where speed, scalability, and scientific creativity are crucial for pandemic response, discoveries like this shine a light on how strategic science can lead the way.
AVITHRAPID project meets HERA
On 3 March 2025, the AVITHRAPID consortium met HERA during the first AVITHRAPID seminar to foster collaboration and explore new opportunities in the domain of antivirals as response against pandemic infectious diseases. During the online meeting, Prof. Bjoern Windshuegel and Prof. Vincenzo Summa of the Consortium led the introduction of activities and services of AVITHRAPID project, with perspectives on advancing in the field of the early and late-stage development of antivirals, while Dr. Joao Madera offered an insight of HERA work and achievements in the framework of a needed end-to-end approach for supporting medical countermeasures from R&D to stockpiling. The seminar was a pivotal opportunity to further invest resources and competences at EU level to prepare for overarching health threat and co-ordinate developments and results. HERA promotes advanced research and innovation to develop effective, safe and affordable countermeasures and in this view the two parts have started a fruitful collaboration. Presentation by Prof. Bjoern Windshuegel Presentation by Prof. Vincenzo Summa
AVITHRAPID Launches ‘AVITHRAPID SEMINARS’ to Advance Pandemic Preparedness and Antiviral Research
AVITHRAPID, the cutting-edge European initiative dedicated to accelerating antiviral research and pandemic preparedness, is proud to announce the launch of AVITHRAPID SEMINARS—a dynamic series of expert-driven discussions uniting regulatory authorities, pharmaceutical industry leaders, European projects, and key stakeholders. The first closed-door seminar is scheduled for Monday, March 3, 2025, featuring a high-level discussion with HERA (DG SANTE), focusing on pandemic preparedness and antiviral strategies.Two public sessions will follow in Summer and Autumn 2025, welcoming industry experts, policymakers, and researchers to exchange insights and shape the future of antiviral preparedness. The press release for the event can be found by clicking here.
Workshop ” Biology and Applications of Extracellular Vesicles”
On Wednesday 12 February 2025, a workshop entitled “Biology and Applications of Extracellular Vesicles” was held in the Aula Magna “Carlo Perone Pacifico”, of the Department of Agricultural and Forestry Sciences, University of Tuscia, partner of Avithrapid consortium. It was organized by Professors Umberto Bernabucci and Nicola Lacetera, as Scientific Directors, respectively, of the PRIN 2022 entitled “Resiliency to heat stress: a system biology approach” and of the PRIN 2022 PNRR entitled “Valorising milk as natural resource for therapeutic purpose: bovine milk Extracellular Vesicles (mEVs) as anti-inflammatory and immunomodulatory agents”. The workshop was organized as part of the activities related to the dissemination and visibility of the project activities of the D.I.Ver.So. department of excellence and it was a good opportunity to introduce AVITHRAPID project as part of the overarching strategy to prepare for future pandemics from different perspectives. Extracellular vesicles play a key role in intercellular communication, both in normal and pathological cellular processes. Numerous studies have highlighted the new opportunities in diagnostics and therapy of these tiny particles, as well as in nutraceuticals, cosmetics and in the veterinary and agricultural fields.
AVITHRAPID Joins Bluesky: A New Space to Connect with the Scientific Community
AVITHRAPID is a project designed to tackle global challenges in antiviral research through an innovative and multidisciplinary approach. Our vision extends beyond laboratory work and scientific publications—we believe in fostering connections, engaging with the scientific community, and sharing our work with a wider audience. For this reason, we are pleased to announce our official presence on Bluesky, a platform that is rapidly becoming an important meeting point for scientists, innovators, and professionals across various disciplines. Why Is AVITHRAPID on Bluesky? In today’s evolving landscape of scientific communication, it is essential to be where meaningful discussions take place, where new ideas emerge, and where strategic collaborations can be built. Bluesky is increasingly recognized among researchers for its open structure and ability to support high-quality scientific interactions. A recent Nature survey found that 70% of respondents already use Bluesky to engage in scientific discussions, stay informed about research advancements, and amplify the visibility of their work. AVITHRAPID aims to be part of this growing ecosystem, bringing its expertise and network into a new space for dialogue and exchange. A New Step in Our Dynamic Communication Strategy At AVITHRAPID, we have always adopted an agile and adaptive approach to communication. Our presence across multiple platforms is a reflection of our commitment to engaging with the scientific and innovation community in the most effective way possible. Joining Bluesky is a strategic extension of this approach, allowing us to: The Role of Social Media in Scientific Communication Recent studies highlight how scientific communication is undergoing a major transformation, with researchers increasingly turning to digital platforms to exchange ideas, build collaborations, and enhance the impact of their discoveries. While specialized academic platforms remain essential for formal scientific discourse, generalist social platforms provide valuable opportunities to increase engagement, connect across disciplines, and reach a broader audience. Digital platforms like Bluesky can facilitate greater accessibility and interdisciplinary dialogue, making scientific discussions more open and dynamic. Join AVITHRAPID on Bluesky As we continue to advance research in antiviral drug discovery, we are committed to expanding the conversation and engaging with a global network of scientists, industry leaders, and policymakers. We invite all those interested in antiviral research and innovation to connect with us. Follow AVITHRAPID on Bluesky: https://bsky.app/profile/avithrapid.bsky.social Use the hashtag #AVITHRAPID to join the discussion. Scientific progress thrives on collaboration and knowledge exchange. Our presence on Bluesky represents an opportunity to strengthen these connections and contribute to an open and engaged research community.
Breaking News: AVITHRAPID Publishes Key Data to Accelerate Drug Development for Dengue
Breaking News: AVITHRAPID Publishes Key Data to Accelerate Drug Development for Dengue AVITHRAPID has announced a breakthrough in the fight against dengue fever by publishing critical protein models for all four dengue virus (DENV) serotypes. These open-access data represent a transformative step in identifying high-potential viral targets for drug development, offering the global scientific community an invaluable resource to combat this widespread and growing threat. The World is in the Grip of a Record Dengue Fever Outbreak: What’s Causing It, and How Can It Be Stopped? Dengue fever, transmitted by the Aedes aegypti mosquito, has emerged as one of the fastest-growing viral threats globally. Once limited to tropical regions, the disease is now spreading to new geographies, including parts of Europe, due to changing climatic conditions, rapid urbanization, and increased global travel. The World Health Organization (WHO) estimates that half the global population is at risk of infection, with severe cases leading to hospitalization or even death. Access here the Global Dengue Surveillance from WHO What makes dengue particularly challenging is its unpredictability: To halt the spread of dengue, an integrated approach is essential: This is where AVITHRAPID steps in with its cutting-edge contributions. AVITHRAPID Efforts: Advancing Drug Development with Open-Access Data As part of its mission to revolutionize antiviral therapeutics, AVITHRAPID has developed a pipeline to model the proteins of all four dengue virus serotypes using the SWISS-MODEL platform. These models are crucial for identifying viral proteins that can serve as promising targets for new drugs, paving the way for innovative treatments. The project team has now made these protein models publicly accessible, enabling researchers and drug developers worldwide to leverage this resource for therapeutic breakthroughs. This open-access initiative not only accelerates scientific discovery but also fosters collaboration across disciplines to combat dengue fever effectively. By providing critical data and computational insights, AVITHRAPID is setting the stage for the development of life-saving therapies, reaffirming its role as a leader in pandemic preparedness and response. Explore the models and join the effort to address this global challenge: Model Archive. AVITHRAPID is funded by the European Union under grant agreement no. 101137192.