Development and Evaluation of Peptidomimetic Compounds against SARS-CoV-2 Spike Protein: An in silico and in vitro Study.

Background: Coronavirus disease 2019 (COVID-19) as global pandemic disease has been adversely affecting public health and social life with considerable loss of human life worldwide. Therefore, there is an urgent need for developing novel therapeutics to combat COVID-19. The causative agent of COVID-19 is SARS-CoV-2 which targets human angiotensin converting enzyme 2 (ACE2) as cellular receptor via its spike (S) protein. In this context, interfering with the binding of SARS-CoV-2 S protein to target molecules could provide a promising strategy to find novel therapeutic agents against SARS-CoV-2. The purpose of the current study was to identify potential peptidomimetics against S protein with a combination of structure-based virtual screening methods and in vitro assays.

Methods: The candidates were inspected in terms of ADME properties, drug-likeness, as well as toxicity profiles. Additionally, molecular docking and dynamics simulations were performed to predict binding of the studied ligands to spike protein.

Results: Biological evaluation of the compounds revealed that PM2 molecule exhibits some antiviral activity.

Conclusion: In summary, this study highlights the importance of combining in silico and in vitro techniques in order to identify antiviral compound to tackle COVID-19 and presents a new scaffold that may be structurally optimized for improved antiviral activity.