Inhibition of novel severe acute respiratory syndrome coronavirus type 2 Mpro by sugarcane polyphenol compound

บทคัดย่อ

Importance of the work: There have been limited studies on high-yield polyphenol sources from
agroindustry by-products for cost-effective novel severe acute respiratory syndrome coronavirus type 2
(SARS-CoV-2) antivirals.
Objectives: To isolate polyphenols from molasses and bagasse, to test their inhibition of SARS-CoV-2 Mpro
and to develop cost-effective antiseptic products.
Materials and Methods: Polyphenols from molasses and bagasse were purified and analyzed using
spectrometry and high-performance liquid chromatography with diode-array detection (HPLC-DAD).
Extracts were tested for SARS-CoV-2 Mpro inhibition, with the concentrations determined required to inhibit
SARS-CoV-2 Mpro activity by 50% (IC50). Each candidate fraction was analyzed using mass spectrometry
and HPLC-DAD. Molecular docking of 12 molecules against SARS-CoV-2 Mpro was conducted using the
GOLD software.
Results: The polyphenol crude extract achieved 100% inhibition of SARS-CoV-2 Mpro at 100 µg/mL, while
fractions 1, 3 and 5 achieved inhibition values (mean ± SE) of 84.15 ± 3.57%, 46.25 ± 13.54% and 29.54 ±
6.14% inhibition, respectively. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) identified
key compounds in fraction 1, including linarin, which produced strong binding in molecular docking studies.
Linarin formed hydrogen bonds with key residues in SARS-CoV-2 Mpro and demonstrated significant
inhibitory activity with a (mean ± SE) IC50 value of 89.98 ± 10.15 µM. Based on these results, linarin, a
naturally occurring flavonoid, could serve as a promising inhibitor of SARS-CoV-2 Mpro.
Main finding: Polyphenol extracts showed substantial SARS-CoV-2 Mpro inhibition, with fraction 1
containing linarin, which had strong binding and inhibitory activity (IC50 of 89.98 ± 10.15 µM). Linarin could
be a promising natural inhibitor against SARS-CoV-2 Mpro.