Plant-Derived Antiviral Compounds as Potential Entry Inhibitors against Spike Protein of SARS-CoV-2 Wild-Type and Delta Variant: An Integrative in SilicoApproach
Jenifer Mallavarpu Ambrose,
Malathi Kullappan,
Shankargouda Patil,
Khalid J. Alzahrani,
Hamsa Jameel Banjer,
Fadi S. I. Qashqari,
A. Thirumal Raj,
Shilpa Bhandi,
Vishnu Priya Veeraraghavan,
Selvaraj Jayaraman,
Durairaj Sekar,
Alok Agarwal,
Korla Swapnavahini,
Surapaneni Krishna Mohan
Affiliations
Jenifer Mallavarpu Ambrose
Department of Research, Panimalar Medical College Hospital & Research Institute, Chennai 600123, India
Malathi Kullappan
Department of Research, Panimalar Medical College Hospital & Research Institute, Chennai 600123, India
Shankargouda Patil
Department of Maxillofacial Surgery and Diagnostic Sciences, Division of Oral Pathology, College of Dentistry, Jazan University, Jazan 45412, Saudi Arabia
Khalid J. Alzahrani
Department of Clinical Laboratories Sciences, College of Applied Medical Sciences, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia
Hamsa Jameel Banjer
Department of Clinical Laboratories Sciences, College of Applied Medical Sciences, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia
Fadi S. I. Qashqari
Department of Microbiology, College of Medicine, Umm Al-Qura University, Makkah 24381, Saudi Arabia
A. Thirumal Raj
Department of Oral Pathology and Microbiology, Sri Venkateswara Dental College and Hospital, Chennai 600130, India
Shilpa Bhandi
Department of Restorative Dental Science, Division of Operative Dentistry, College of Dentistry, Jazan University, Jazan 45142, Saudi Arabia
Vishnu Priya Veeraraghavan
Centre of Molecular Medicine and Diagnostics (COMManD), Department of Biochemistry, Saveetha Dental College, Saveetha Institute of Medical and Technical Sciences (SIMATS), Saveetha University, Chennai 600077, India
Selvaraj Jayaraman
Centre of Molecular Medicine and Diagnostics (COMManD), Department of Biochemistry, Saveetha Dental College, Saveetha Institute of Medical and Technical Sciences (SIMATS), Saveetha University, Chennai 600077, India
Durairaj Sekar
Centre for Cellular and Molecular Research, Saveetha Dental College & Hospitals, Saveetha Institute of Medical & Technical Sciences (SIMATS), Saveetha University, Chennai 600077, India
Alok Agarwal
Department of Chemistry, Chinmaya Degree College, BHEL Haridwar 249403, India
Korla Swapnavahini
Department of Biotechnology, Dr B.R. Ambedkar University, Etcherla, Srikakulam 532410, India
Surapaneni Krishna Mohan
Departments of Biochemistry, Molecular Virology, Research, and Clinical Skills & Simulation, Panimalar Medical College Hospital & Research Institute, Chennai 600123, India
The wild-type SARS-CoV-2 has continuously evolved into several variants with increased transmissibility and virulence. The Delta variant which was initially identified in India created a devastating impact throughout the country during the second wave. While the efficacy of the existing vaccines against the latest SARS-CoV-2 variants remains unclear, extensive research is being carried out to develop potential antiviral drugs through approaches like in silico screening and drug-repurposing. This study aimed to conduct the docking-based virtual screening of 50 potential phytochemical compounds against a Spike glycoprotein of the wild-type and the Delta SARS-CoV-2 variant. Subsequently, molecular docking was performed for the five best compounds, such as Lupeol, Betulin, Hypericin, Corilagin, and Geraniin, along with synthetic controls. From the results obtained, it was evident that Lupeol exhibited a remarkable binding affinity towards the wild-type Spike protein (−8.54 kcal/mol), while Betulin showed significant binding interactions with the mutated Spike protein (−8.83 kcal/mol), respectively. The binding energy values of the selected plant compounds were slightly higher than that of the controls. Key hydrogen bonding and hydrophobic interactions of the resulting complexes were visualized, which explained their greater binding affinity against the target proteins—the Delta S protein of SARS-CoV-2, in particular. The lower RMSD, the RMSF values of the complexes and the ligands, Rg, H-bonds, and the binding free energies of the complexes together revealed the stability of the complexes and significant binding affinities of the ligands towards the target proteins. Our study suggests that Lupeol and Betulin could be considered as potential ligands for SARS-CoV-2 spike antagonists. Further experimental validations might provide new insights for the possible antiviral therapeutic interventions of the identified lead compounds and their analogs against COVID-19 infection.
