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Antiviral Screening Compound Libraries

Addressing viral diseases through antiviral drugs and vaccines remains an ongoing challenge due to the vast array of diseases caused by viruses and the absence of universal treatments. The initial hurdle in antiviral drug discovery is the diversity of virus serotypes, making our efforts to tackle the problem even more complicated. Treatment failure often occurs due to drug resistance emerging from virus mutations. Additionally, most viral metabolic processes overlap with those of host cells, resulting in greater complexities in developing selective antiviral drugs. Fortunately, certain viral enzymes and multifunctional viral proteins, such as capsid proteins, do not exist in human cells, which enables us to use them as attractive targets for antiviral drug development.

In 2022, emphasizing the acute need for new antiviral medical products, the World Health Organization reported that more than 630,000 individuals worldwide died of HIV-related illnesses [1]. Chronic hepatitis C infection, as of 2019 data, contributes to around 400,000 annual deaths. Hepatitis B, also in 2019, was responsible for an estimated 820,000 deaths, primarily resulting from cirrhosis and hepatocellular carcinoma. Furthermore, in 2019, the world faced a pandemic caused by SARS-CoV-2, with the global death toll from COVID-19 surpassing 6 million [2]. These statistics bring to the forefront the development of potent antiviral drugs capable of combating the constantly changing nature of virus genomes.

Pursuing its research within the most pressing domains of medicinal chemistry, our cheminformatics team has created a specialized collection of non-overlapping Antiviral Libraries designed for high throughput screening (HTS) and high content screening (HCS) drug discovery projects. The Rule of Five (Ro5) compliance is indicated for each compound. In total, these Screening Sets comprise over 13,700 drug-like screening compounds with potential antiviral activity:

Furthermore, we offer an expanded Merged Antiviral Screening Superset, encompassing more than 40,000 small-molecule compounds that include individual screening subsets for various viral diseases, all consolidated in one resource:

For detailed information on each dedicated screening set, as well as separate SD files, please refer to the respective links provided above.

The compound selection can be customized based on your requirements, cherry picking is available.

Please, contact us at orders@lifechemicals.com for any additional information and price quotations.

You can also be interested in the following related products:
 

Antiviral Library by 2D Similarity

This Antiviral Screening Compound Library was designed with 2D fingerprint similarity search against the reference set of 41,514 biologically active compounds (IC50, Ki, etc. less than 10 μM, Inhibition > 25%) from therapeutically relevant viral assays representing different virus species and their proteins of interest (extracted from Binding and ChEMBL databases): 

  • Bovine viral diarrhea virus
  • Cowpox virus
  • Coxsackievirus
  • Cytomegalovirus
  • Dengue virus
  • Echovirus
  • Enterovirus
  • Felid herpesvirus
  • Hepatitis virus
  • Human adenovirus
  • Human coxsackievirus
  • Human echovirus
  • Human enterovirus
  • Human herpesvirus
  • Human immunodeficiency virus
  • Human papillomavirus
  • Human parainfluenza virus
  • Human poliovirus
  • Human rhinovirus
  • Influenza virus
  • Japanese encephalitis virus
  • La Crosse virus
  • Lassa virus
  • Mammalian orthoreovirus
  • Measles virus
  • Modoc virus
  • Moloney murine sarcoma virus
  • Murine hepatitis virus
  • Poliovirus
  • Punta Toro virus
  • Reovirus
  • Respiratory syncytial virus
  • Rotavirus
  • San Angelo virus
  • SARS coronavirus
  • Semliki forest virus
  • Simian immunodeficiency virus
  • Sindbis virus
  • Tobacco mosaic virus
  • Transmissible gastroenteritis virus
  • Vaccinia virus
  • Venezuelan equine encephalitis virus
  • Vesicular stomatitis virus
  • West Nile virus
  • Woodchuck hepatitis virus
  • Yellow fever virus 

After filtering and merging their activity type data, the resulting 19,244 unique compounds were obtained and used as a basis for the Library design.

Then, the Life Chemicals HTS Compound Collection was filtered for analogs of molecules with known activity against different virus species and viral targets, using Tanimoto 80 % similarity cut-off on MDL public keys fingerprints. Applying a combination of the organism- and single protein-type research data, we created two subsets, with the first one containing almost 6,000 small-molecule analogs against virus organisms and the second one including 4,200 compounds targeting viral proteins (Fig. 1).

In total,over 10,150 unique structurally diverse compounds were selected for the Life Chemicals Antiviral Library by 2D Similarity

A

 Distribution of compounds from the LC Antiviral Library by 2D Similarity according to different virus types and their targets

B

Distribution of compounds from the LC Antiviral Library by 2D Similarity according to different virus types (A) and their targets (B).

Figure 1. Distribution of compounds from the Antiviral Library by 2D Similarity according to different virus types (A) and their targets (B).

Antiviral Library by Combined Ligand-Based and Structure-Based Approaches

In order to identify key features of a protein-ligand binding mechanism, the relevant protein crystal structures of the most interesting and widely spread antiviral molecular targets were first collected from the RCSB Protein Data Bank. Selected target examples are shown below:

  • SARS coronavirus 3C-like proteinase
  • Human rhinovirus A protease
  • Human immunodeficiency virus type 1 reverse transcriptase
  • Human immunodeficiency virus type 1 integrase
  • Human herpesvirus 6 DNA polymerase 
  • Human herpesvirus 5 DNA polymerase
  • Human herpesvirus 5 capsid protein P40
  • Hepatitis C virus NS5B RNA-dependent RNA polymerase
  • Hepatitis C virus NS3 protease
  • Dengue virus type 2 NS3 protein

The reference set of antiviral molecules was then extracted from the ChEMBLdb (v26). The compounds with the highest reported antiviral activity (IC50 less than 1–1.5 uM) against each target were clustered. The top compounds from each group were docked into the corresponding target’s crystal structure to obtain bioactive conformation.

For the targets with unresolved structures, bioactive conformations of inhibitors were predicted with the rigid alignment of generated conformers and statistical analysis. These aligned structures were further used for pharmacophore modeling in silico. Both Glide docking and UNITY pharmacophore search methods were employed to select the most promising antiviral-associated compounds (Fig. 2).

Combined ligand-based and structure-based approaches, employed for the design of this Antiviral Library, provide the method cross-validation and a higher degree of accuracy. As a result, over 3,500 potential antiviral agents were identified within the Life Chemicals HTS Compound Collection (Fig. 3). All PAINs and reactive compounds were excluded from the selection by in-house MedChem filters.

CHEMBL93512 inhibitor of NS3 protease/helicase

Figure 2. Example of the reference compound CHEMBL93512, an inhibitor of NS3 protease/helicase, (left) and its conformers (right). The desired pharmacophore features located on atomic centers of the native ligand are highlighted, e.g., hydrophobic centers in red. 

Distribution of compounds related to the selected RCSB PDB structures in the Life Chemicals Antiviral Library by Combined Ligand-Based and Structure-Based Approaches

Figure 3. Distribution of compounds related to the selected RCSB PDB structures in the Life Chemicals Antiviral Library by Combined Ligand-Based and Structure-Based Approaches

References:

  1. World Health Organization. https://www.who.int/
  2. Aleem A, Akbar Samad AB, Vaqar S. Emerging Variants of SARS-CoV-2 and Novel Therapeutics Against Coronavirus (COVID-19) [Updated 2023 May 8]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK570580/
  3. De Clercq E, Li G. Approved Antiviral Drugs over the Past 50 Years // Clin Microbiol Rev. 2016 Jul;29(3):695-747. doi: 10.1128/CMR.00102-15.
  4. Frange P, Leruez-Ville M. Maribavir, brincidofovir and letermovir: Efficacy and safety of new antiviral drugs for treating cytomegalovirus infections // Med Mal Infect. 2018 Dec;48(8):495-502. doi: 10.1016/j.medmal.2018.03.006.
  5. Nováková L, Pavlík J, Chrenková L, Martinec O, Červený L. Current antiviral drugs and their analysis in biological materials-Part I: Antivirals against respiratory and herpes viruses // J Pharm Biomed Anal. 2018 Jan 5;147:400-416. doi: 10.1016/j.jpba.2017.06.071.
  6. Mantero M, Rogliani P, Cazzola M, Blasi F, Di Pasquale M. Emerging antibacterial and antiviral drugs for treating respiratory tract infections // Expert Opin Emerg Drugs. 2018 Sep;23(3):185-199. doi: 10.1080/14728214.2018.1504020.
  7. Zumla A, Chan JF, Azhar EI, Hui DS, Yuen KY. Coronaviruses - drug discovery and therapeutic options // Nat Rev Drug Discov. 2016 May;15(5):327-47. doi: 10.1038/nrd.2015.37.
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