SEARCH · PubMed Health

Results for “Antiviral hits”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

4 recordsLinked to original sources

PubMed2027

Screening of Antiviral Agents Against CHIKV Using Reporter Virus.

Chikungunya virus (CHIKV) causes a disease characterized by chronic musculoskeletal inflammation for which specific antivirals are not yet available. Currently, a supportive therapy to alleviate fever and pain is used, but it does not limit viral replication or the persistence of chronic arthritis symptoms. Thus, the identification and development of new active molecules against CHIKV is urgently needed. Here, we present a cell-based methodology that enables the implementation of a rapid and cost-effective strategy for high- and medium-throughput screening (HTS) of compounds, including repurposed drugs or novel molecules. This methodology allows for the identification of novel antiviral hits with a good activity and selectivity profile against CHIKV.

Antiviral Agents↗

PubMed2026

Quantitative Fluorescence Imaging of Alphavirus Infection for Antiviral Screenings.

Fluorescence microscopy offers a highly sensitive and versatile approach for investigating alphavirus infection at the cellular level. By combining fluorescently labeled viruses with quantitative image analysis, this method enables detailed spatial and temporal characterization of infection dynamics, including the detection of subtle differences in replication kinetics and cell-to-cell spread. A central aim of this protocol is its application in antiviral screening assays. Image-based quantification of fluorescence intensity provides a robust and reproducible means to assess the efficacy of antiviral compounds, allowing early and sensitive detection of inhibitory effects in infected cells. This facilitates the identification of promising antiviral hits and supports the evaluation of dose-dependent responses. The approach is also well-suited for comparative studies of different alphavirus strains or mutants, as variations in replication behavior and dissemination patterns become readily apparent. Its flexibility, compatibility with multiple cell lines, and straightforward integration into automated imaging platforms makes the method scalable and suitable for high-throughput screening campaigns. Overall, this protocol advances the discovery and evaluation of antiviral strategies. Given that several alphaviruses cause significant human and veterinary diseases, lack approved antiviral therapies, and continue to expand geographically with emerging outbreaks, the identification of novel antivirals remains an urgent priority. Therefore, this fluorescence-based workflow represents a valuable and timely contribution to modern alphavirus research.

Antiviral Agents↗

PubMed2025

Structure-based discovery of inhibitors of Mac1 domain of nonstructural protein-3 of SARS-CoV-2 by machine learning-augmented screening of chemical space.

Significant efforts have been recently dedicated to the discovery of small molecule inhibitors against the Macrodomain 1 (Mac1) of nonstructural protein 3 (NSP3) as potential antivirals for SARS-CoV-2. Thus, Mac1 has also been selected as the target for the Critical Assessment of Hit-finding Experiments (CACHE) challenge #3. As contestants in that challenge, we developed a computational strategy that ranked on the top among all 23 participants in the competition and resulted in the discovery of a novel chemical series of non-charged Mac1 inhibitors. Those have been identified through the combination of machine learning-accelerated virtual screening of Enamine REAL Diversity Subset of approximately 25 million compounds and consequent hit expansion into the entire Enamine REAL Space library. In particular, the initially identified hit compound CACHE3-HI_1706_56 (KD = 20 μM) was explored by probing 17 close analogues from a library of 44 billion molecules from the Enamine REAL. All those analogues effectively displaced the Mac1-binding ADP-ribose peptide, and 12 were confirmed to engage with Mac1 by the Surface Plasmon Resonance experiments, revealing a new chemical series of compounds for hit-to-lead optimization. The structure of the CACHE3-HI_1706_56-Mac1 complex was further determined at high resolution with crystallography, confirming initial computational predictions. Our results illustrate the effectiveness of ML-accelerated docking to rapidly identify novel chemical series and provide a strong foundation for the development of SARS-CoV-2 NSP3 Mac1 inhibitors.

CACHE challenge↗

PubMed2026

Dual HBV cccDNA-linked HiBiT reporter hepatocyte models for screening of candidate cccDNA modulators.

Chronic hepatitis B remains difficult to cure because the viral covalently closed circular DNA (cccDNA) minichromosome can persist and sustain viral transcription, creating a need for scalable, reporter readouts that facilitate early discovery of cccDNA-modulating agents. Here, we developed two complementary hepatocyte HiBiT reporter models: a replication-competent HBV reporter in HepaRG cells (HepaRG-Hibit16), in which a secreted split-NanoLuc HiBiT signal is linked to cccDNA-associated expression, and a Cre/Lox-based recombinant cccDNA (rcccDNA) reporter in HepG2 cells (HepG2-Rccc1a) that rapidly generates rcccDNA with a matched HiBiT readout. Screening of 1,403 FDA-approved compounds across both models identified 13 concordant, non-cytotoxic hits. Palovarotene, a retinoic acid receptor-γ agonist, was selected as an exemplar concordant hit and reduced HBV antigens, HBV DNA, and cccDNA and inhibited HBV infection in multiple hepatocyte-based in vitro systems without overt cytotoxicity at the tested concentrations. Together, this dual-reporter strategy supports efficient cross-model triage of candidate cccDNA modulators for subsequent orthogonal validation.

Humans↗