Title
Authors
Nikita Chordia Golchha1, Hasanain Abdulhameed Odhar2, Anand Nighojkar3 & Sadhana Nighojkar *,4
Affiliation
1School of Biotechnology, Devi Ahilya University, Takshashila Campus, Khandwa Road, INDORE-452001, India; 2Department of Pharmacy, Al-Zahrawi University College, Karbala, Iraq; 3Maharaja Ranjit Singh College of Professional Sciences, Hemkunt Campus, Khandwa Road, Indore, 452001, India; 4Mata Gujri College of Professional Studies, A.B. Road, Indore, 452001, India
Nikita Chordia Golchha - E-mail: nikita.chordia25@gmail.com
Hasanain Abdulhameed Odhar - E-mail: hodhar3@gmail.com
Anand Nighojkar - E-mail: nanandphd@gmail.com
Sadhana Nighojkar - E-mail: sadhana0301@gmail.com
Article Type
Research Article
Date
Received January 1, 2024; Revised January 31, 2024; Accepted January 31, 2024, Published January 31, 2024
Abstract
The opportunistic pathogen, Clostridioides difficile owes its extreme pathogenicity for its ability to develop antibiotic resistance and recurrent infections. The current antibiotics used for the treatment are showing declining sensitivity and rising antibiotic resistance. Therefore, it is of interest to develop the anti-clostridial drugs to overcome these issues. Hence, we have explored ZINC library to find the suitable lead compounds against five target proteins of C. difficile. Multistep virtual screening is performed to find the suitable compounds that are checked for their stability using molecular dynamics and are validated in vitro against C. difficile. In our study, five compounds viz., ZINC64969876, ZINC13641164, ZINC13691348, ZINC5554596 and ZINC3894278 that inhibit HisC, Spo0A, PdcA, DAHP synthase and cyclic-di GMP proteins, respectively have been identified. Further, these compounds were tested in vitro against four different isolates of C. difficile and all of them were found to inhibit the pathogen. However, to use these compounds as anti-clostridial drugs, further testing needs to be done. The selected compounds from our study are reported for the first time as antimicrobial agents against C. difficile.
Keywords
Clostridioides difficile, inhibition, pathogen, compounds, in silico, molecular docking, dynamics, in vitro.
Citation
Golchha et al. Bioinformation 20(1): 39-48 (2024)
Edited by
P Kangueane
ISSN
0973-2063
Publisher
License
This is an Open Access article which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. This is distributed under the terms of the Creative Commons Attribution License.
