ACE-2-derived Biomimetic Peptides for the Inhibition of Spike Protein of SARS-CoV-2

SARS-CoV-2, a novel coronavirus causing overwhelming death and infection worldwide, has emerged as a pandemic. Compared to its predecessor SARS-CoV, SARS-CoV-2 is more infective for being highly contagious and exhibiting tighter binding with host angiotensin-converting enzyme 2 (hACE-2). The entry of the virus into host cells is mediated by the interaction of its spike protein with hACE-2. Thus, a peptide that has a resemblance to hACE-2 but can overpower the spike protein-hACE-2 interaction will be a potential therapeutic to contain this virus. The non-interacting residues in the receptor-binding domain of hACE-2 have been mutated to generate a library of 136 new peptides. Out of this library, docking and virtual screening discover seven peptides that can exert a stronger interaction with the spike protein than hACE-2. A peptide derived from simultaneous mutation of all the non-interacting residues of hACE-2 yields two-fold stronger interaction than hACE-2 and thus turns out here to be the best peptide-inhibitor of the novel coronavirus. The binding of the spike protein and the best peptide-inhibitor with hACE-2 is explored further by molecular dynamics, free energy, and principal component analysis to demonstrate its efficacy. Further, the inhibition assay study with the best peptide inhibitor is in progress..

Medienart:

Preprint

Erscheinungsjahr:

2021

Erschienen:

2021

Enthalten in:

chemRxiv.org - (2021) vom: 17. Nov. Zur Gesamtaufnahme - year:2021

Sprache:

Englisch

Beteiligte Personen:

Panda, Saroj Kumar [VerfasserIn]
Gupta, Parth Sarthi Sen [VerfasserIn]
Biswal, Satyaranjan [VerfasserIn]
Ray, Abhik Kumar [VerfasserIn]
Rana, Malay Kumar [VerfasserIn]

Links:

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Themen:

540
Chemistry

doi:

10.26434/chemrxiv.12335933

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

XCH017931657