Computational analysis and validation of UGT1A1/4 missense variants impacting tecovirimat metabolism in monkeypox patients.
PMID 42369683 | PMCID PMC13293890 | DOI 10.3389/fsysb.2026.1821230 · Frontiers in systems biology · 2026
INTRODUCTION: Single nucleotide polymorphisms (SNPs) in genes encoding drug-metabolizing enzymes can significantly impact a patient's response to medication. Uridine diphosphate glucuronosyltransferase 1 family A1 and A4 (UGT1A1/4) are crucial enzymes for metabolizing tecovirimat, the first oral antiviral drug approved for treating the monkeypox virus. METHODS: This study used a comprehensive in-silico workflow to assess the deleterious effects of 842 missense mutations and 308 SNPs in the non-coding regions of the UGT1A1 gene, alongside 700 missense mutations and 324 SNPs in the non-coding regions of the UGT1A4 gene. An ensemble of in-silico prediction, structural modelling, and docking tools was employed. RESULTS: We identified six missense variants that may compromise the structural integrity and function of the UGT1A1/4 enzymes. Specifically, the UGT1A1 SNPs G308R, P356T and G374S, while in UGT1A4 the SNPs G309R, P357T and G375S, were predicted to be the most harmful missense SNPs. DISCUSSION: These mutations could affect drug-enzyme binding, potentially altering tecovirimat's therapeutic efficacy.
Validated evidence
| Type | Entity | Source evidence | Confidence | Extractor |
|---|---|---|---|---|
| gene | UGT1A1 | “Computational analysis and validation of UGT1A1/4 missense variants impacting tecovirimat metabolism in monkeypox patients.” | 0.98 | hgnc_dict_v1 |
| gene | UGT1A4 | “METHODS: This study used a comprehensive in-silico workflow to assess the deleterious effects of 842 missense mutations and 308 SNPs in the non-coding regions of the UGT1A1 gene, alongside 700 missense mutations and 324 SNPs in the non-coding regions of the UGT1A4 gene.” | 0.98 | hgnc_dict_v1 |
| population | Population | “Uridine diphosphate glucuronosyltransferase 1 family A1 and A4 (UGT1A1/4) are crucial enzymes for metabolizing tecovirimat, the first oral antiviral drug approved for treating the monkeypox virus.” | 0.80 | saudi_context_rules_v1 |
| variant | G308R | “Specifically, the UGT1A1 SNPs G308R, P356T and G374S, while in UGT1A4 the SNPs G309R, P357T and G375S, were predicted to be the most harmful missense SNPs.” | 0.82 | literature_variant_regex_v2 |
| variant | P356T | “Specifically, the UGT1A1 SNPs G308R, P356T and G374S, while in UGT1A4 the SNPs G309R, P357T and G375S, were predicted to be the most harmful missense SNPs.” | 0.82 | literature_variant_regex_v2 |
| variant | G374S | “Specifically, the UGT1A1 SNPs G308R, P356T and G374S, while in UGT1A4 the SNPs G309R, P357T and G375S, were predicted to be the most harmful missense SNPs.” | 0.82 | literature_variant_regex_v2 |
| variant | G309R | “Specifically, the UGT1A1 SNPs G308R, P356T and G374S, while in UGT1A4 the SNPs G309R, P357T and G375S, were predicted to be the most harmful missense SNPs.” | 0.82 | literature_variant_regex_v2 |
| variant | P357T | “Specifically, the UGT1A1 SNPs G308R, P356T and G374S, while in UGT1A4 the SNPs G309R, P357T and G375S, were predicted to be the most harmful missense SNPs.” | 0.82 | literature_variant_regex_v2 |
| variant | G375S | “Specifically, the UGT1A1 SNPs G308R, P356T and G374S, while in UGT1A4 the SNPs G309R, P357T and G375S, were predicted to be the most harmful missense SNPs.” | 0.82 | literature_variant_regex_v2 |