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ORIGINAL RESEARCH article

Front. Cell. Infect. Microbiol.
Sec. Antibiotic Resistance and New Antimicrobial drugs
Volume 14 - 2024 | doi: 10.3389/fcimb.2024.1422500

In silico testing to identify compounds that inhibit ClfA and ClfB binding to the host for the formulation of future drugs against Staphylococcus aureus colonization and infection

Provisionally accepted
Shila Singh Shila Singh 1Minakshi Bhattacharjee Minakshi Bhattacharjee 1*Balagopalan Unni Balagopalan Unni 1Rajpal S. Kashyap Rajpal S. Kashyap 2Abdul Malik Abdul Malik 3Suhail Akhtar Suhail Akhtar 4
  • 1 Assam Down Town University, Dispur, India
  • 2 Central India Institute of Medical Sciences, Nagpur, Maharashtra, India
  • 3 King Saud University, Riyadh, Riyadh, Saudi Arabia
  • 4 A.T. Still University, Kirksville, Missouri, United States

The final, formatted version of the article will be published soon.

    Staphylococcus aureus is a highly resistant pathogen. It has multiple virulence factors, which makes it one of the most pathogenic bacteria for humankind. The vast increase in antibiotic resistance in these bacteria is a warning of existing healthcare policies. Most of the available antibiotics are ineffective due to resistance; this situation requires the development of drugs that target specific proteins and are not susceptible to resistance. In this study, we identified a compound that acts as an antagonist of ClfA and ClfB by inhibiting their binding to host cells. The shortlisted compound's binding activity was tested by docking and molecular dynamics during its interaction with proteins. The identified compound has excellent binding energy with both ClfA (-10.11 kcal/mol) and ClfB (-11.11 kcal/mol). The molecular dynamics of the protein and compound were stable and promising for further in vitro and in vivo tests. The performance of our compound was tested and compared with that of the control molecule allantodapsone, which was reported in a previous study as a pan inhibitor of the clumping factor. An ADMET study of our selected compound revealed its reliable drug likeliness. This compound is an ideal candidate for in vitro studies.

    Keywords: Staphylococcus aureus, Clumping factor, adhesin binding protein, Antimicrobial resistance (AMR), colonization, Molecular Docking & Molecular Dynamics (MD) simulation

    Received: 24 Apr 2024; Accepted: 30 Aug 2024.

    Copyright: © 2024 Singh, Bhattacharjee, Unni, Kashyap, Malik and Akhtar. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Minakshi Bhattacharjee, Assam Down Town University, Dispur, 781006, India

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.