ChemDiv library of potential small molecule antiviral compounds comprises 87,000 compounds
The development of antiviral compounds is a critical frontier in both medicine and science. In the face of emerging and re-emerging viral threats, such as Coronavirus, HIV, Influenza, and Hepatitis C Virus (HCV), the need for effective antiviral therapies has never been more pressing. These compounds play a pivotal role in managing and treating infections, reducing mortality rates, and improving the quality of life for millions globally. Moreover, antiviral drug discovery contributes significantly to our understanding of viral mechanisms and pathogenesis, leading to more innovative and targeted therapeutic approaches.
The current small molecule library is a result of extensive research and innovative methodologies, including analysis of isosteric and bioisosteric transformations, identification of hot spots and crucial binding points, and implementation of scaffold hopping. The library incorporates 2D/3D topological similarities and fingerprints, along with scaffold priority profiling, to ensure a diverse and comprehensive collection of compounds. The focus on novel chemistry and scaffold prioritization has led to the inclusion of a wide range of molecules, targeting key proteins in viruses such as
- Mpro, PLpro, RdRp for Coronavirus;
- Revertase, NL4-3, Fusion, Integrases for HIV;
- Neuraminidase, NS1, NSA1 for Influenza;
- NS3 Helicase, NS3/A4 protease, NS5A, NS5B for HCV.
This strategic approach enhances the likelihood of discovering potent antiviral agents with unique modes of action.
At its core, the library is built upon a foundation of advanced chemical analysis and molecular biology techniques. Key methodologies include:
- Isosteric and Bioisosteric Transformations. These techniques involve replacing one part of a molecule with another that has a similar physical or chemical property, while maintaining biological activity. This approach is crucial in modifying the pharmacokinetic and pharmacodynamic profiles of molecules, thereby enhancing their efficacy and reducing potential side effects.
- Hot Spots and Crucial Binding Points Identification. The library is curated by analyzing molecular interactions at the atomic level, identifying hot spots and crucial binding points that are critical for viral protein functionality. By targeting these specific areas, the compounds in the library show a high potential for disrupting viral life cycles effectively.
- Scaffold Hopping. This strategy involves jumping from one chemical scaffold to another while preserving the essential features that contribute to biological activity. Scaffold hopping aids in the discovery of novel structures that might offer improved properties over existing molecules, such as increased potency, selectivity, or better pharmacokinetic profiles.
- 2D/3D Topological Similarities and Fingerprints. Utilizing both two-dimensional and three-dimensional analyses, the library encompasses a broad range of molecular shapes and structures. This diversity ensures the targeting of a wide spectrum of viral proteins, offering multiple points of intervention in the viral replication process.
- Scaffold Priority Profiling. The library emphasizes the prioritization of scaffolds based on novel chemistry, ensuring that each compound brings a unique aspect to antiviral research. This approach facilitates the exploration of uncharted chemical spaces, leading to the potential discovery of groundbreaking antiviral agents.
The small molecule library offers immense benefits for research and pharmaceutical companies. Its extensive coverage of diverse viral targets, including those from Coronavirus, HIV, Influenza, HCV, and more, makes it an invaluable tool for drug discovery and development. The library's focus on innovative chemistry and prioritized scaffolds accelerates the identification of novel drug candidates with potential for high efficacy and specificity. Additionally, the structured approach to molecule selection, based on cutting-edge scientific principles, reduces the time and cost associated with the early stages of drug discovery. For pharmaceutical companies, this library represents a significant resource for expanding their antiviral pipeline and responding rapidly to emerging viral threats. For researchers, it provides a robust platform for exploring novel antiviral mechanisms and contributing to the advancement of medical science.