Abstract: The combination of cephalosporins and alcohol, commonly known as “taking cephalosporin with alcohol”, has frequently led to clinical tragedies. Traditionally, this is attributed to the inhibition of aldehyde dehydrogenase 2 (ALDH2) by the methylthiotetrazole or methyltriazine side chains present in certain cephalosporin antibiotics, resulting in acetaldehyde accumulation and toxicity (disulfiram-like reaction). However, recent clinical cases show that evencephalosporins lacking these side chains, such as ceftazidime, can cause acetaldehyde accumulation, suggesting a potential new mechanism that the existing explanation does not cover. During the lecture, the authors inspired students to apply computational simulation tools to explore everyday chemical phenomena, such as the “cephalosporin with alcohol” scenario. This study uses molecular docking, molecular dynamics simulation, and molecular mechanics Poisson-Boltzmann surface area (MMPBSA) calculations to investigate binding modes of cephoperazone, ceftriaxone, and ceftazidime with ALDH2, uncovering a new mechanism of interaction between cephalosporins and ALDH2. This case study not only provides a deeper scientific explanation of the popular online phrase "taking cephalosporin with alcohol is danger to health" but also encourages students to explore the scientific basis of everyday chemical phenomena. More importantly, it offers novel insights and theoretical evidence for the molecular mechanisms underlying clinical tragedies caused by cephalosporin-alcohol interactions.

Key words: Cephalosporin antibiotics, Aldehyde dehydrogenase 2, Molecular docking, Molecular dynamics simulation, Life chemistry