Biomedical subjects

Dong Han

Publications and source records attributed to Dong Han.

4 recordsLinked to original sources

PubMed2026

Remdesivir maintains antiviral potency against clinically relevant SARS-CoV-2 Nsp12 substitutions.

Remdesivir (RDV) is a nucleotide analog prodrug approved for COVID-19 treatment that inhibits the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp; nsp12). Although RDV maintains activity against circulating variants of concern, ongoing evaluation of resistance-associated substitutions is critical for clinical care, particularly in settings of prolonged viral replication such as immunocompromised individuals. We assessed the phenotypic impact of nsp12 substitutions identified from in vitro resistance selection, RDV clinical reports, and global sequence surveillance. Using a recombinant infectious SARS-CoV-2 reporter virus, we compared susceptibility of these nsp12 substitutions to RDV and its parent nucleoside, GS-441524. After confirming concordant resistance profiles between RDV and GS-441524, we assessed RDV susceptibility in a complementary non-infectious replicon system. In both systems, single nsp12 substitutions remained fully susceptible to RDV within their respective assay variability limits. Of the double substitutions tested, S759A/V792I conferred the largest reduction in antiviral susceptibility (∼15-fold) but was associated with impaired replication kinetics. Given the strong concordance between the two assays, the replicon system also enabled phenotypic characterization of substitutions E802A, E802D, and P323L/E802D that could not be rescued as infectious virus. Analysis of >17 million SARS-CoV-2 genomes in GISAID showed that all tested nsp12 substitutions had low prevalence (≤0.1%), except P323L (98.8%). Collectively, these data reinforce the high genetic barrier to RDV resistance, as reduced susceptibility is typically accompanied by substantial reductions in replication. Our findings support the continued clinical utility of RDV and highlight the complementary value of SARS-CoV-2 infectious virus and replicon systems for antiviral resistance surveillance and phenotyping.

COVID-19↗

PubMed2026

Adaptive Evolution of the PFK Gene Family in Chinese Longsnout Catfish, Leiocassis longirostris.

The Chinese longsnout catfish is a typical carnivorous fish with a relatively weak ability to utilize glucose. However, the genomic basis for its glucose metabolic adaptation remains unclear. In this study, we used comparative genomics methods to systematically analyze the evolutionary characteristics of glucose metabolism-related genes in the Chinese longsnout catfish, focusing on gene family evolution, patterns of expansion and contraction, and selective pressures. The results indicate that glucose metabolism-related genes have undergone significant reshaping during evolution. Genes involved in glucose digestion, absorption, and insulin signaling pathways demonstrate a tendency toward contraction, while those associated with protein and lipid metabolism exhibit expansion. This pattern is consistent with the species' long-term adaptation to a high-protein, high-fat diet. Comparative analysis further revealed that, compared to fish with different dietary habits, certain key genes involved in glycolysis in the Chinese longsnout catfish exhibit a reduction in copy number. Molecular evolutionary analysis showed that key genes involved in glycolysis and gluconeogenesis (including hexokinase 2 (hk2), phosphofructokinase, muscle/platelet (pfkm/p)) exhibit signs of accelerated evolution or positive selection. Notably, the PFK gene family exhibits complex evolutionary characteristics resulting from the combined effects of gene contraction, rapid evolution, and positive selection. In summary, this study reveals the genomic evolutionary basis for the glucose metabolic adaptation of the Chinese longsnout catfish and identifies the PFK gene family as a key candidate for elucidating its unique glucose metabolic characteristics.

Leiocassis longirostris↗

PubMed2026

Prenatal SNP-array chromosomal microarray analysis in 3,549 pregnancies: indication-specific yields and clinical implications.

BACKGROUND: SNP-based chromosomal microarray analysis (CMA) is widely used in invasive prenatal diagnosis, yet real-world performance across contemporary referral pathways, especially in the NIPT era, remains incompletely characterized. METHODS: We retrospectively analyzed 3,549 prenatal invasive samples tested by SNP array, and evaluated diagnostic yield overall and by referral indication and ultrasound phenotype. RESULTS: In total, we identified 398 pathogenic or likely pathogenic (P/LP) variants across 386 fetuses, resulting in an overall diagnostic yield of 10.9% (386/3,549). These findings comprised 223 aneuploidies and 175 pathogenic CNVs. In contrast, variants of uncertain significance (VOUS) were detected in 12.0% (426/3,549) of cases. Diagnostic yields were heavily stratified by indication: yields peaked in NIPT high-risk referrals (38.9%) and were intermediate in ultrasound-based cases (~ 11%), but dropped significantly in the advanced maternal age (AMA; 4.2%) and serum screening (~ 5-6%) groups. Conversely, VOUS rates remained remarkably stable across all referral categories. Sub-analysis of ultrasound abnormalities revealed that multisystem anomalies conferred the highest risk (27.3%), driven predominantly by aneuploidies; among soft markers, increased nuchal translucency (NT) emerged as the strongest predictor of chromosomal pathology. CONCLUSIONS: In our cohort, SNP-array identified clinically actionable findings in 10.9% of cases. NIPT enriched diagnostic yields, particularly for aneuploidies, and NT thickness was strongly associated with pathogenic findings. These results support an indication-based approach to genomic testing, with NIPT as a triage tool for aneuploidy and CMA for high-risk populations, while improving VOUS counseling.

Humans↗

PubMed2024

No Remdesivir Resistance Observed in the Phase 3 Severe and Moderate COVID-19 SIMPLE Trials.

Remdesivir (RDV) is a broad-spectrum nucleotide analog prodrug approved for the treatment of COVID-19 in hospitalized and non-hospitalized patients with clinical benefit demonstrated in multiple Phase 3 trials. Here we present SARS-CoV-2 resistance analyses from the Phase 3 SIMPLE clinical studies evaluating RDV in hospitalized participants with severe or moderate COVID-19 disease. The severe and moderate studies enrolled participants with radiologic evidence of pneumonia and a room-air oxygen saturation of ≤94% or >94%, respectively. Virology sample collection was optional in the study protocols. Sequencing and related viral load data were obtained retrospectively from participants at a subset of study sites with local sequencing capabilities (10 of 183 sites) at timepoints with detectable viral load. Among participants with both baseline and post-baseline sequencing data treated with RDV, emergent Nsp12 substitutions were observed in 4 of 19 (21%) participants in the severe study and none of the 2 participants in the moderate study. The following 5 substitutions emerged: T76I, A526V, A554V, E665K, and C697F. The substitutions T76I, A526V, A554V, and C697F had an EC50 fold change of ≤1.5 relative to the wildtype reference using a SARS-CoV-2 subgenomic replicon system, indicating no significant change in the susceptibility to RDV. The phenotyping of E665K could not be determined due to a lack of replication. These data reveal no evidence of relevant resistance emergence and further confirm the established efficacy profile of RDV with a high resistance barrier in COVID-19 patients.

Humans↗