Structure-based drug discovery to identify SARS-CoV2 spike protein–ACE2 interaction inhibitors

Abstract

After the emergence of the COVID-19 pandemic in late 2019, the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has undergone a dynamic evolution driven by the acquisition of genetic modifications, resulting in several variants that are further classified as variants of interest (VOIs), variants under monitoring (VUM) and variants of concern (VOC) by World Health Organization (WHO). Currently, there are five SARS-CoV-2 VOCs (Alpha, Beta, Delta, Gamma and Omicron), two VOIs (Lambda and Mu) and several other VOIs that have been reported globally. In this study, we report a natural compound, Curcumin, as the potential inhibitor to the interactions between receptor binding domain (RBD(S1)) and human angiotensin-converting enzyme 2 (hACE2) domains and showcased its inhibitory potential for the Delta and Omicron variants through a computational approach by implementing state of the art methods. The study for the first time revealed a higher efficiency of Curcumin, especially for hindering the interaction between RBD(S1) and hACE-2 domains of Delta and Omicron variants as compared to other lead compounds. We investigated that the mutations in the RBD(S1) of VOC especially Delta and Omicron variants affect its structure compared to that of the wild type and other variants and therefore altered its binding to the hACE2 receptor. Molecular docking and molecular dynamics (MD) simulation analyses substantially supported the findings in terms of the stability of the docked complexes. This study offers compelling evidence, warranting a more in-depth exploration into the impact of these alterations on the binding of identified drug molecules with the Spike protein. Further investigation into their potential therapeutic effects in vivo is highly recommended.

Communicated by Ramaswamy H. Sarma

Keywords:

• SARS-CoV-2
• COVID-19
• variants of concern
• computational approach
• molecular docking
• MD simulation
• curcumin

Acknowledgments

RK, MC and DS highly acknowledge the support from Department of Biotechnology, Govt. of India (Grant Number: BT/PR40153/BTIS/137/8/2021) for Bioinformatics Facility at Dr. B.R. Ambedkar Center for Biomedical Research. RK gratefully acknowledges Indian Council of Medical Research (ICMR) for awarding him the Senior Research Fellowship (Grant Number: HIV/STI/17/02/2022-ECD-II). Rahul Kaushik is thankful to Biotechnology Research Center, Technology Innovation Institute, Abu Dhabi, UAE for its support and resources.

Authors’ contribution

Conceptualization: Ravi Kant, Rahul Kaushik, Daman Saluja and Madhu Chopra. Methodology: Ravi Kant, Rahul Kaushik, Daman Saluja and MadhuChopra. Software, Formal Analysis, Data Curation, Writing original draft: Ravi Kant, Rahul Kaushik and Daman Saluja. Writing – review and editing: Daman Saluja and Madhu Chopra. Supervision: Daman Saluja and Madhu Chopra.

Disclosure statement

The authors declare that there is no conflict of interest.

Data availability statement

Data is available upon request to the corresponding author.

Additional information

Funding

This work was supported by Department of Biotechnology (Grant Number: BT/PR40153/BTIS/137/8/2021), Ministry of Science and Technology, India, Indian Council of Medical Research (ICMR) and (Grant Number: HIV/STI/17/02/2022-ECD-II).