Abstract
Vibrio cholerae causes the diarrheal disease cholera which affects millions of people globally. The outer membrane protein U (OmpU) is the outer membrane protein that is most prevalent in V. cholerae and has already been recognized as a critical component of pathogenicity involved in host cell contact and as being necessary for the survival of pathogenic V. cholerae in the host body. Computational approaches were used in this study to screen a total of 37,709 natural compounds from the traditional Chinese medicine (TCM) database against the active site of OmpU. Following a sequential screening of the TCM database, we report three lead compounds—ZINC06494587, ZINC85510056, and ZINC95910434—that bind strongly to OmpU, with binding affinity values of −8.92, −8.12, and −8.78 kcal/mol, which were higher than the control ligand (−7.0 kcal/mol). To optimize the interaction, several 100 ns molecular dynamics simulations were performed, and the resulting complexes were shown to be stable in their vicinity. Additionally, these compounds were predicted to have good drug-like properties based on physicochemical properties and ADMET assessments. This study suggests that further research be conducted on these compounds to determine their potential use as cholera disease treatment.
Highlights
Cholera is a severe diarrheal infection caused by consuming food or water contaminated with the bacteria Vibrio cholerae
Binding pocket residues of the outer membrane protein U (OmpU) protein were predicted as Gly32, Asn34, Gln35, Ser36, Gly37, Asp38, Lys39, Ala40, Gly41, Glu53, Gly55, Arg76, Leu80, Val92, Phe94, Glu96, Arg116, Tyr117, Tyr119, Glu128, Thr130, Asn134, Asp135, Gly136, Ala137, Gly139, Val140, Thr142, Asp143, Asp146, Asn153, Lys158, Ala162, Asn163, Arg164, Ala170, Tyr171, Lys172, Lys181, Ala182, Ser183, and Tyr312 (Figure 1)
OmpU is a crucial virulence component of V. cholerae that is engaged in host cell interaction and is necessary for the survival of pathogenic V. cholerae in the host body
Summary
Cholera is a severe diarrheal infection caused by consuming food or water contaminated with the bacteria Vibrio cholerae It remains a global public health problem, as well as a manifestation of injustice and a lack of social development. V. cholerae, as with the majority of Gram-negative bacteria, produces outer membrane vesicles during growth, which entrap the periplasm and transmit bacterial DNA [4]. It produces a diverse set of outer membrane proteins (OMPs) with varying component molecular masses. Among these OMPs, OmpU and OmpT have been thoroughly investigated in terms of virulence, adhesion, and host colonization [5]. OmpU possesses porin properties and has been shown to provide bile and antibacterial peptide resistance to the bacterium [9]
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