Molecular dynamic simulation reveals spider antimicrobial peptide Latarcin-1 and human eosinophil cationic protein as peptide inhibitors of SARS-CoV-2 variants

Abstract

COVID-19 has rapidly proliferated around 180 countries, and new cases are reported frequently. No peptide medication has been developed that can reliably block SARS-CoV-2 infection. The investigation focuses on the crucial host receptors angiotensin-converting enzyme 2 (ACE2) , which can bind receptor-binding domain (RBD) on the SARS-CoV-2 spike protein (S). To investigate the inhibitory effects of human Eosinophil Cationic Protein (hECP) and Latarcin-1 (L1)on SARS-CoV-2 infection, we have selected them as research subjects. Further, we ran extensive molecular dynamics simulations to bring the docked peptide-ACE2 complex into its equilibrium state. The outcomes were then evaluated with g_MMPBSA and interaction analysis. We have also considered the Delta and Omicron variants to examine these peptides’ inhibitory effects. The experimental findings revealed an enhanced capability of L1 and hECP as SARS-CoV-2 inhibitors, occupying hot spots and numerous key residues in ACE2. These include ASP30, ASP38, GLU35 and GLU75, which significantly inhibit the binding of RBD and ACE2 and are effective against two common variants in a similar manner. In addition, this study can serve as a springboard for future research on SARS-CoV-2 inhibitors.

Communicated by Ramaswamy H. Sarma

Keywords:

• SARS-CoV-2
• peptide inhibitors
• ACE2
• variants
• molecular dynamics

Disclosure statement

Our study is based on open source data, so there are no conflicts of interest.

Additional information

Funding

This work was supported by Shanghai Agriculture Applied Technology Development Program, China (Grant No.X2021-02-08-00-12-F00782), the Science and Technology Commission of Shanghai Municipality (Grant: 19430750600). The work also was supported by Open Funding Project of State Key Laboratory of Microbial Metabolism (MMLKF21-11).