Designing Self-Inhibitory fusion peptide analogous to viral spike protein against novel severe acute respiratory syndrome (SARS-CoV-2)

Abstract

COVID-19 is a highly contagious viral infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is declared pandemic by the World Health Organization (WHO). The spike protein of SARS-CoV-2 is a key component playing a pivotal role in facilitating viral fusion as well as release of genome into the host cell. Till date there is no clinically approved vaccine or drug available against Covid-19. We designed four hydrophobic inhibitory peptides (ITPs) based on WWIHS (Wimley and White interfacial hydrophobicity scale) score, targeting the HR1 domain of spike protein. Two inhibitory peptides out of four have a strong affinity to the hydrophobic surface of HR1 domain in pre-fusion spike protein. The MD simulation result showed the strong accommodation of ITPs with HR1 domain surface. These self-inhibitory peptides mimic the function of HR2 by binding to HR1 domain, thus inhibiting the formation of HR1-HR2 post-fusion complex, which is a key structure for virus-host tropism.

Communicated by Ramaswamy H. Sarma

Proposed mechanism of inhibitory peptides against Covid-19.

Keywords:

• Covid-19
• SARS-CoV-2
• Spike protein
• Inhibitory peptides
• WWIHS

Acknowledgements

We acknowledge the Galaxy platform and Gromacs for providing the software facility to conduct this computational work.

Disclosure statement

The authors have declared that no conflict of interests exist.

Authors’ contributions

IS, and SS conceived and designed research. SS and IS conducted the computational experiments and analyzed the data. SS, IS and KKO conducted molecular dynamics and analyzed the results. IS and SS wrote the manuscript. All the authors read and approved the manuscript.