en Microbial pathogenesis Microbial pathogenesis Original article Original article <b><span style="font-size:10.0pt"><span style="line-height:107%"><span new="" roman="" style="font-family:" times="">Introduction:</span></span></span></b><span style="font-size:10.0pt"><span style="line-height:107%"><span new="" roman="" style="font-family:" times=""> Cholera is a highly contagious disease that causes severe diarrhea and dehydration. This study investigated podophyllotoxin, deoxypodophyllotoxin, and ursolic acid as inhibitors of <i>tcpA</i>, <i>ompW,</i> and </span></span></span><i><span style="font-size:10.0pt"><span style="line-height:107%"><span new="" roman="" style="font-family:" times="">ctxB</span></span></span> </i><span style="font-size:10.0pt"><span style="line-height:107%"><span new="" roman="" style="font-family:" times="">genes in <i>Vibrio cholerae</i>.<b> Methods:</b> We obtained the crystallized structure of podophyllotoxin, deoxypodophyllotoxin, and ursolic acid from the PubChem database for use as a ligand. The mm² method in Chem3D v20.1.1.125 was used to optimize the structure of the ligands. We used AutodackVina v.1.2.0 to evaluate the ligands as inhibitors against the active site of the <i>tcpA</i>, <i>ompW</i>, and <i>ctxB</i> proteins. The output results were analyzed and assessed by BIOVIA Discovery Studio 2016 V16.1.0 X64.<b> Results:</b> The reported affinities ranged from -6.8 and -8.7 kcal/mol. The highest diversity of links was found in <i>tcpA</i> and <i>ctxB</i>. Hydrogen bonds were established with Threonine (91, 111), Glycine (113, 114, 94), and Alanine (92) of <i>tcpA</i>, indicating the effectiveness of ligands against <i>tcpA</i>. The ligands podophyllotoxin, deoxypodophyllotoxin, and ursolic acid showed a variety of hydrogen bonds against <i>ompW</i> and <i>ctxB</i>, respectively, with Arginine, Isoleucine, Histidine, Glycine, and Glutamine. These results demonstrate the excellent inhibitory effects of the ligands against <i>Vibrio cholerae</i>.<b> Conclusion:</b> <i>Vibrio cholerae</i> plays a crucial role in causing pandemic cholera in humans. The predicted conformations of the ligands in this study showed that podophyllotoxin and deoxypodophyllotoxin have higher inhibitory potential than ursolic acid. Therefore, podophyllotoxin and deoxypodophyllotoxin can be potential agents for further research in developing Anti-Vibrio cholerae drugs.</span></span></span> Vibrio cholerae, Ursolic Acid, Podophyllotoxin, tcpA, ompW 41 48 http://jommid.pasteur.ac.ir/browse.php?a_code=A-10-391-1&slc_lang=en&sid=1 Yasin SarveAhrabi yasin.ahrabi2016@gmail.com 0000-0001-7062-6963 Yes Department of Biology, Central Tehran Branch, Islamic Azad University, Tehran, Iran Ovis Rostamiyan Ovisrostamian@gmail.com https://orcid.org/0000-0002-4362-5524 No Department of Biology, Central Tehran Branch, Islamic Azad University, Tehran, Iran Sarina Nejati Khoei sarina.nejati.kh@gmail.com 0000-0001-9630-4911 No Department of Biology, Central Tehran Branch, Islamic Azad University, Tehran, Iran