Identification of potential SARS-CoV-2 Nsp1 inhibitors from Piper sarmentosum Roxb. using molecular docking.

Abstract

Nsp1 in SARS-CoV-2 is a key protein that increases the virus's pathogenicity and virulence by binding to the host ribosome and blocks the 40S ribosomal subunit channel, which effectively impedes the mRNA translation as well as crippling the host immune system. Previous studies revealed that the N-terminal in Nsp1 is part and parcel of Nsp1 efficiency, and mutations in its core residues have weakened the protein's. This knowledge persuades us to carry out the in silico screening on plant compounds of Piper sarmentosum Roxb. against the five target residues which are Glu36, Glu37, Arg99, Arg124 and Lys125. Potential compounds were tested for their druggability. As a result, we identified five out of 112 compounds including stigmasterol, N-feruloyltyramine, beta-Sitosterol, 13-(1,3-benzodioxol-5-yl)- N-(2methylpropyl) trideca-2,4,12-trienamide and N-(2-methylpropyl) octadeca-2-4dienamide in Piper sarmentosum Roxb. as potential inhibitors for Nsp1. These compounds formed at least a hydrophobic, hydrogen bonding or π-cation interactions with the protein. Furthermore, SwissADME analysis and the number of bindings to the target residues suggest that N-feruloyltyramine is the ideal inhibitor candidate against SARS-CoV-2 at its N-terminal of Nsp1. Lastly, the interaction with N-feruloyltyramine increased flexibility in the loop regions of N-terminal Nsp1, especially residues 54 to 70, with residue 59 showing the highest fluctuation, potentially affecting the protein's stability and function due to the correlation between RMSF and protein function.