Affiliations 

  • 1 Faculty of Pharmacy, Sanata Dharma University, Campus III, Paingan, Maguwoharjo, Depok, Sleman 55282, Yogyakarta, Indonesia
  • 2 Chemistry Department, Faculty of Mathematics and Natural Sciences, Padjadjaran University, Jatinangor, Sumedang 45363, West Java, Indonesia
  • 3 Malaysian Institute of Pharmaceuticals and Nutraceuticals, National Institute of Biotechnology Malaysia, Halaman Bukit Gambir, 11900 Bayan Lepas, Pulau Pinang, Malaysia
  • 4 Pharmaceutical Technology Department, School of Pharmaceutical Sciences and USM-RIKEN Centre for Ageing Science (URICAS), Universiti Sains Malaysia, 11800 Minden, Pulau Pinang, Malaysia
Results Chem, 2021 Jan;3:100195.
PMID: 34567959 DOI: 10.1016/j.rechem.2021.100195

Abstract

This present study reports some natural products and one hydroxamic acid synthetic compound which were previously reported as matrix metalloproteinase-9 (MMP-9) inhibitors to be evaluated for their inhibition toward severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) 3-chymotrypsin-like protease (3CLpro). This enzyme is one of the proteins responsible for this coronaviral replication. Two herbal methanolic extracts i.e., Averrhoa carambola leaves and Ageratum conyzoides aerial part demonstrate >50% inhibition at 1000 µg/mL. Interestingly, apigenin, one of flavonoids, demonstrates 92% inhibition at 250 µg/mL (925 µM) as well as hydroxamic acid compound, N-isobutyl-N-(4-methoxyphenylsulfonyl)glycyl hydroxamic acid (NNGH), which shows 69% inhibition at 100 µM. The in vitro results are supported by the docking studies revealing that the binding mode of both compounds is mainly by interacting with GLU166 residue in the hydrophobic pocket of the 3CLpro. Pharmacophore mapping further supported the results by confirming that the in vitro activities of both compounds are due to their pharmacophore features employing hydrogen bond acceptor (HBA), hydrogen bond donor (HBD) and hydrophobic. Gas Chromatography-Mass Spectrometry (GC-MS) analysis reported chromene compounds in Ageratum conyzoides aerial part methanolic extract are potential to be this enzyme inhibitor candidate. These all results reflect their potencies to be SARS-CoV-2 inhibitors through 3CLpro inhibition mechanism.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.