Detail Cantuman

ABSTRACT
Xiamycin is a pentacyclic indolosesquiterpenoid derived from mangrove endophytes was studied
in vitro to inhibit the replication of porcine epidemic diarrhea virus and human immunodeficiency
virus. This study aimed to examine the potential pharmacological activity of xiamycin derivatives
as an inhibitor of SARS-CoV-2 virus replication through molecular docking and analyze their
pharmacokinetic and toxicity profiles.
The selection of comparison pharmaceutical agents used ChemDes. Xiamycin derivatives as test
compounds and molnupiravir as inhibitors were screened for Lipinski's Rule of Five. The
identification of RdRp as a molecular target was confirmed through the PASSonline program. The
RdRp receptor was selected based on an assessment of receptor quality via the RCSB PDB and
PDBsum. Minimization energy used Avogadro and Swiss PDB programs. Receptor and ligand were
docked by Autodock. Visualization of molecular docking results with Biovia and Pymol. ADMET
profile assessment using the ADMETlab 2.0 program.
This study shows that xiamycin E had the highest pharmacological potential compared to other
xiamycin derivatives and molnupiravir with an energy affinity of -6.92 kcal/mol, an inhibitory
constant of 8.41 M, and knows three key amino acid residues in the NiRAN domain, namely amino
acid ASN 209, LYS 50, and ASP 218. ADMET prediction shows that xiamycin E is ideal for certain
parameters and not ideal for certain parameters.
The xiamycin derivatives have the potential to be developed as an antiviral. Optimization of
xiamycin E as a candidate for the RdRp inhibitor of SARS-CoV-2 requires further studies related
to the structure tissue exposure/selectivity activity relationship.
Keywords: molecular docking, xiamycin, RdRp, SARS-CoV-2