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Prophylactic potential of kelulut honey against SARS-CoV-2 via ACE-2 binding inhibition

Ismail, Azlini and Ismail, Che Muhammad Khairul Hisyam and Abdul Hamid, Azzmer Azzar and Mohd Abdul Razak, Mohd Ridzuan and Mokhtar@Makhtar, Khairani Idah and Mustafa Al-Ahmad, Basma Ezzat and Lestari, Widya (2025) Prophylactic potential of kelulut honey against SARS-CoV-2 via ACE-2 binding inhibition. In: UNSPECIFIED.

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Abstract

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global health crisis. Despite vaccination efforts, the virus continues to evolve, decreasing the effectiveness of current vaccines. Angiotensin-converting enzyme 2 (ACE-2) is a crucial protein that facilitates SARS-CoV-2 entry into host cells. Our prior in silico docking and molecular dynamics simulation studies indicated that a compound called 4,4’-Stilbenedicarboxamidine (SDC) binds strongly to ACE-2, surpassing MLN 4760, a known ACE-2 inhibitor. This study aims to assess the potential of local kelulut honey (KH) and SDC in inhibiting the spike protein-ACE-2 interaction. Methods: An ELISA assay using the SARS-CoV-2 S1 RBD: ACE-2 Inhibitory Screening Assay Kit (BPS Bioscience, US) was performed following the manufacturer’s instructions. KH and SDC were tested at multiple concentrations in triplicate, with MLN 4760 serving as the reference. Results: KH, MLN 4760, and SDC significantly inhibited spike-ACE-2 binding, with an Emax of 82.66 ± 0.24 %, 59.81 ± 8.00 %, and 19.74 ± 0.40 %, respectively. The IC50 values of KH, MLN 4760, and SDC were 0.17 % (v/v), 55.44 μM, and 19.20 μM, respectively. At 100 μM, SDC was found to inhibit spike-ACE-2 binding by 19.74 %, which was significantly lower (P<0.05) than MLN 4760 at 59.81%. Conclusions: KH inhibits the interaction between the spike protein and ACE-2, supporting its prophylactic use against SARS-CoV-2. The higher inhibitory efficacy of KH in its absolute form compared to SDC is presumably due to the interaction of multiple bioactive constituents in KH, rather than the effect of SDC alone.

Item Type: Proceeding Paper (Poster)
Uncontrolled Keywords: Kelulut Honey; Honey; Stingless Bee; Malaysia; Bioactive Compound; COVID-19; ACE-2; ACE2; Angiotensin Converting Enzyme
Subjects: R Medicine > RM Therapeutics. Pharmacology
R Medicine > RM Therapeutics. Pharmacology > RM300 Drugs and their action
R Medicine > RS Pharmacy and materia medica
Kulliyyahs/Centres/Divisions/Institutes (Can select more than one option. Press CONTROL button): Kulliyyah of Dentistry
Kulliyyah of Dentistry > Department of Fundamental Dental and Medical Sciences
Kulliyyah of Science
Kulliyyah of Science > Department of Biotechnology
Depositing User: AP. Ts DR. AZLINI ISMAIL
Date Deposited: 25 Jan 2026 10:47
Last Modified: 25 Jan 2026 10:47
Queue Number: 2026-01-Q1760
URI: http://irep.iium.edu.my/id/eprint/126976

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