Geranii Herba as a Potential Inhibitor of SARS-CoV-2 Main 3CLpro, Spike RBD, and Regulation of Unfolded Protein Response: An In Silico Approach

Selvaraj Arokiyaraj; Antony Stalin; Balakrishnan Senthamarai Kannan; Hakdong Shin

doi:10.3390/antibiotics9120863

Geranii Herba as a Potential Inhibitor of SARS-CoV-2 Main 3CL^pro, Spike RBD, and Regulation of Unfolded Protein Response: An In Silico Approach

Antibiotics (Basel). 2020 Dec 3;9(12):863. doi: 10.3390/antibiotics9120863.

Authors

Selvaraj Arokiyaraj¹, Antony Stalin², Balakrishnan Senthamarai Kannan³, Hakdong Shin¹

Affiliations

¹ Department of Food Science & Biotechnology, Sejong University, Seoul 05006, Korea.
² State Key Laboratory of Subtropical Silviculture, Department of Traditional Chinese Medicine, Zhejiang A&F University, Hangzhou 311300, China.
³ Department of Chemistry, Tirunelveli Dakshina Mara Nadar Sangam (TDMNS) College, Valliyur, Tirunelveli 627113, Tamil Nadu, India.

Abstract

Background: Since the first patient identified with SARS-CoV-2 symptoms in December 2019, the trend of a spreading coronavirus disease 2019 (COVID-19) infection has remained to date. As for now, there is an urgent need to develop novel drugs or vaccines for the SARS-CoV-2 virus.

Methods: Polyphenolic compounds have potential as drug candidates for various diseases, including viral infections. In this study, polyphenolic compounds contained in Geranii Herba were chosen for an in silico approach. The SARS-CoV-2 receptor-binding domain (RBD), 3CL^pro (Replicase polyprotein 1ab), and the cell surface receptor glucose-regulated protein 78 (GRP78) were chosen as target proteins.

Results: Based on the molecular docking analysis, ellagic acid, gallic acid, geraniin, kaempferitrin, kaempferol, and quercetin showed significant binding interactions with the target proteins. Besides, the molecular dynamic simulation studies support Geranii Herba's inhibition efficiency on the SARS-CoV-2 RBD. We assume that the active compounds in Geranii Herba might inhibit SARS-CoV-2 cell entry through the ACE2 receptor and inhibit the proteolytic process. Besides, these compounds may help to regulate the cell signaling under the unfolded protein response in endoplasmic reticulum stress through the binding with GRP78 and avoid the SARS-CoV-2 interaction.

Conclusions: Hence, the compounds present in Geranii Herba could be used as possible drug candidates for the prevention/treatment of SARS-CoV-2 infection.

Keywords: 3CLpro; GRP78; Geranii Herba; RBD; SARS-CoV-2; docking; polyphenols.