Investigating the antiviral therapeutic potentialities of marine polycyclic lamellarin pyrrole alkaloids as promising inhibitors for SARS-CoV-2 and Zika main proteases (Mpro)

Abstract

The new coronavirus variant (SARS-CoV-2) and Zika virus are two world-wide health pandemics. Along history, natural products-based drugs have always crucially recognized as a main source of valuable medications. Considering the SARS-CoV-2 and Zika main proteases (Mpro) as the re-production key element of the viral cycle and its main target, herein we report an intensive computer-aided virtual screening for a focused list of 39 marine lamellarins pyrrole alkaloids, against SARS-CoV-2 and Zika main proteases (Mpro) using a set of combined modern computational methodologies including molecular docking (MDock), molecule dynamic simulations (MDS) and structure-activity relationships (SARs) as well. Indeed, the molecular docking studies had revealed four promising marine alkaloids including [lamellarin H (14)/K (17)] and [lamellarin S (26)/Z (39)], according to their notable ligand-protein energy scores and relevant binding affinities with the SARS-CoV-2 and Zika (Mpro) pocket residues, respectively. Consequentially, these four chemical hits were further examined thermodynamically though investigating their MD simulations at 100 ns, where they showed prominent stability within the accommodated (Mpro) pockets. Moreover, in-deep SARs studies suggested the crucial roles of the rigid fused polycyclic ring system, particularly aromatic A- and F- rings, position of the phenolic -OH and δ-lactone functionalities as essential structural and pharmacophoric features. Finally, these four promising lamellarins alkaloids were investigated for their in-silico ADME using the SWISS ADME platform, where they displayed appropriated drug-likeness properties. Such motivating outcomes are greatly recommending further in vitro/vivo examinations regarding those lamellarins pyrrole alkaloids (LPAs).

Communicated by Ramaswamy H. Sarma

KEYWORDS:

• SARS-CoV-2
• Zika virus
• antiviral
• marine sponges
• lamellarins alkaloids
• molecular docking
• dynamics simulation

Acknowledgments

Amr El-Demerdash is immensely grateful to his home university, Mansoura University, Egypt, for the unlimited support inside and outside. The authors thank Tobin Florio (http://flozbox-science.com/) for scientific illustrations for Figures 1 and 2. Amr El-Demerdash is immensely grateful to the John Innes Centre, Norwich Research Park, United Kingdom for the postdoctoral fellowship. Florbela Pereira would like to thank Fundacão para a Ciência e a Tecnologia, MCTES, in the scope of the project UIDB/50006/2020 of the Research Unit, Associate Laboratory for Green Chemistry, LAQV

Disclosure statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Credits of authorship contribution

Conceptualization: Florbela Pereira, Reem K. Arafa and Amr El-Demerdash. Validation: Florbela Pereira, Reem K. Arafa and Amr El-Demerdash. Formal analysis: Florbela Pereira, Reem K. Arafa and Amr El-Demerdash. Investigation: Florbela Pereira, Loay Bedda, Mohamed A. Tammam, Abdul Kader Alabdullah, Reem K. Arafa and Amr El-Demerdash. Resources: Florbela Pereira, Loay Bedda, Mohamed A. Tammam, Abdul Kader Alabdullah, Reem K. Arafa and Amr El-Demerdash. Data curation: Florbela Pereira, Reem K. Arafa and Amr El-Demerdash. Writing original draft: Florbela Pereira, Loay Bedda, Mohamed A. Tammam, Abdul Kader Alabdullah, Reem K. Arafa and Amr El-Demerdash. Writing-review & editing: Florbela Pereira, Loay Bedda, Mohamed A. Tammam, Abdul Kader Alabdullah, Reem K. Arafa and Amr El-Demerdash.

Additional information

Funding

Amr El-Demerdash is immensely grateful to the John Innes Centre, Norwich Research Park, United Kingdom, for the postdoctoral fellowship. Florbela Pereira would like to thank Fundacão para a Ciência e a Tecnologia, MCTES, in the scope of the project UIDB/50006/2020 of the Research Unit, Associate Laboratory for Green Chemistry, LAQV.