2. Academic Validation
  3. Structural, dynamic behaviour, in-vitro and computational investigations of Schiff's bases of 1,3-diphenyl urea derivatives against SARS-CoV-2 spike protein

Structural, dynamic behaviour, in-vitro and computational investigations of Schiff's bases of 1,3-diphenyl urea derivatives against SARS-CoV-2 spike protein

  • Sci Rep. 2024 Jun 1;14(1):12588. doi: 10.1038/s41598-024-63345-9.
Saeed Ullah 1,  Atta Ullah 1,  Muhammad Waqas 1,  Sobia Ahsan Halim 1,  Anam Rubbab Pasha 1 2,  Zahid Shafiq 3,  Suraj N Mali 4,  Rahul D Jawarkar 5,  Ajmal Khan 6,  Asaad Khalid 7,  Ashraf N Abdalla 8,  Hamdy Kashtoh 9,  Ahmed Al-Harrasi 10
Affiliations

Affiliations

  • 1 Natural and Medical Sciences Research Center, University of Nizwa, Birkat-ul-Mouz 616, Nizwa, Sultanate of Oman.
  • 2 Institute of Chemical Sciences, Bahauddin Zakariya University, Multan, 60800, Pakistan.
  • 3 Institute of Chemical Sciences, Bahauddin Zakariya University, Multan, 60800, Pakistan. zahidshafiq@bzu.edu.pk.
  • 4 School of Pharmacy, D.Y. Patil University (Deemed to be University), Sector 7, Nerul, Navi Mumbai, 400706, India.
  • 5 Department of Medicinal Chemistry and Drug Discovery, Dr. Rajendra Gode Institute of Pharmacy, University Mardi Road, Amravati, 444603, India.
  • 6 Natural and Medical Sciences Research Center, University of Nizwa, Birkat-ul-Mouz 616, Nizwa, Sultanate of Oman. ajmalkhan@unizwa.edu.om.
  • 7 Substance Abuse and Toxicology Research Center, Jazan University, P.O. Box: 114, 45142, Jazan, Saudi Arabia.
  • 8 Department of Pharmacology and Toxicology, College of Pharmacy, Umm Al-Qura University, 21955, Makkah, Saudi Arabia.
  • 9 Department of Biotechnology, Yeungnam University, Gyeongsan, 38541, Gyeongbuk, Republic of Korea. hamdy_kashtoh@ynu.ac.kr.
  • 10 Natural and Medical Sciences Research Center, University of Nizwa, Birkat-ul-Mouz 616, Nizwa, Sultanate of Oman. aharrasi@unizwa.edu.om.
PMID: 38822113 DOI: 10.1038/s41598-024-63345-9
Abstract

The COVID-19 has had a significant influence on people's lives across the world. The viral genome has undergone numerous unanticipated changes that have given rise to new varieties, raising alarm on a global scale. Bioactive phytochemicals derived from nature and synthetic sources possess lot of potential as pathogenic virus inhibitors. The goal of the recent study is to report new inhibitors of Schiff bases of 1,3-dipheny urea derivatives against SARS COV-2 spike protein through in-vitro and in-silico approach. Total 14 compounds were evaluated, surprisingly, all the compounds showed strong inhibition with inhibitory values between 79.60% and 96.00% inhibition. Here, compounds 3a (96.00%), 3d (89.60%), 3e (84.30%), 3f (86.20%), 3g (88.30%), 3h (86.80%), 3k (82.10%), 3l (90.10%), 3m (93.49%), 3n (85.64%), and 3o (81.79%) exhibited high inhibitory potential against SARS COV-2 spike protein. While 3c also showed significant inhibitory potential with 79.60% inhibition. The molecular docking of these compounds revealed excellent fitting of molecules in the spike protein receptor binding domain (RBD) with good interactions with the key residues of RBD and docking scores ranging from - 4.73 to - 5.60 kcal/mol. Furthermore, molecular dynamics simulation for 150 ns indicated a strong stability of a complex 3a:6MOJ. These findings obtained from the in-vitro and in-silico study reflect higher potency of the Schiff bases of 1,3-diphenyl urea derivatives. Furthermore, also highlight their medicinal importance for the treatment of SARS COV-2 Infection. Therefore, these small molecules could be a possible drug candidate.

Keywords

1,3-Diphenyl urea; Docking; In silico studies; MD simulation; SARS COV-2 spike protein; Schiff’s bases.

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