Screening of inhibitors against SARS-CoV-2 spike protein and their capability to block the viral entry mechanism: A viroinformatics study

Abd-ElAziem Farouk; Mohammad Hassan Baig; Mohd Imran Khan; Taehwan Park; Saqer S Alotaibi; Jae-June Dong

doi:10.1016/j.sjbs.2021.02.066

Screening of inhibitors against SARS-CoV-2 spike protein and their capability to block the viral entry mechanism: A viroinformatics study

Saudi J Biol Sci. 2021 Jun;28(6):3262-3269. doi: 10.1016/j.sjbs.2021.02.066. Epub 2021 Feb 26.

Authors

Abd-ElAziem Farouk¹, Mohammad Hassan Baig², Mohd Imran Khan³, Taehwan Park⁴, Saqer S Alotaibi¹, Jae-June Dong²

Affiliations

¹ Department of Biotechnology, College of Science, P.O. Box 11099, Taif, 21944, Saudi Arabia.
² Department of Family Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.
³ Department of Biophysics, All India Institute of Medical Sciences, New Delhi, India.
⁴ University-Industry Foundation, Yonsei University College of Medicine, Seoul, Republic of Korea.

Abstract

SARS-CoV-2, previously named 2019 novel coronavirus (2019-nCoV), has been associated with the global pandemic of acute respiratory distress syndrome. First reported in December 2019 in the Wuhan province of China, this new RNA virus has several folds higher transmission among humans than its other family member (SARS-CoV and MERS-CoV). The SARS-CoV-2 spike receptor-binding domain (RBD) is the region mediating the binding of the virus to host cells via Angiotensin-converting enzyme 2 (ACE2), a critical step of viral. Here in this study, we have utilized in silico approach for the virtual screening of antiviral library extracted from the Asinex database against the Receptor binding domain (RBD) of the S1 subunit of the SARS-CoV-2 spike glycoprotein. Further, the molecules were ranked based on their binding affinity against RBD, and the top 15 molecules were selected. The affinity of these selected molecules to interrupt the ACE2-Spike interaction was also studied. It was found that the chosen molecules were demonstrating excellent binding affinity against spike protein, and these molecules were also very effectively interrupting the ACE2-RBD interaction. Furthermore, molecular dynamics (MD) simulation studies were utilized to investigate the top 3 selected molecules' stability in the ACE2-RBD complexes. To the best of our knowledge, this is the first study where molecules' inhibitory potential against the Receptor binding domain (RBD) of the S1 subunit of the SARS-CoV-2 spike glycoprotein and their inhibitory potential against the ACE2-Spike has been studied. We believe that these compounds can be further tested as a potential therapeutic option against COVID-19.

Keywords: ACE2; ACE2, Angiotensin-converting enzyme 2; Antiviral drugs; COVID-19, Coronavirus Disease 2019; CoVs, Coronaviruses; In silico; MD, Molecular dynamics; MERS, Middle East respiratory syndrome coronavirus; RBD; RBD, Receptor-binding domain; RMSD, Root mean square deviation; RMSF, Root mean square fluctuation; SARS, Severe acute respiratory syndrome; SARS-CoV-2.