A novel inhibitor of SARS-CoV infection: Lactulose octasulfate interferes with ACE2-Spike protein binding

Rami Adel Pashameah; Raya Soltane; Ahmed M Sayed

doi:10.1016/j.heliyon.2023.e23222

A novel inhibitor of SARS-CoV infection: Lactulose octasulfate interferes with ACE2-Spike protein binding

Heliyon. 2023 Dec 3;10(1):e23222. doi: 10.1016/j.heliyon.2023.e23222. eCollection 2024 Jan 15.

Authors

Rami Adel Pashameah¹, Raya Soltane², Ahmed M Sayed^{3

4}

Affiliations

¹ Department of Chemistry, Faculty of Applied Science, Umm Al-Qura University, Makkah 21955, Saudi Arabia.
² Department of Biology, Adham University College, Umm Al-Qura University, Makkah 21955, Saudi Arabia.
³ Department of Pharmacognosy, Faculty of Pharmacy, Nahda University, 62513 Beni-Suef, Egypt.
⁴ Department of Pharmacognosy, collage of Pharmacy, Almaaqal University, 61014 Basra, Iraq.

Abstract

The ongoing challenge of managing coronaviruses, particularly SARS-CoV-2, necessitates the development of effective antiviral agents. This study introduces Lactulose octasulfate (LOS), a sulfated disaccharide, demonstrating significant antiviral activity against key coronaviruses including SARS-CoV-2, SARS-CoV, and MERS-CoV. We hypothesize LOS operates extracellularly, targeting the ACE2-S-protein axis, due to its low cellular permeability. Our investigation combines biolayer interferometry (BLI), isothermal titration calorimetry (ITC)-based experiments with in silico studies, revealing LOS's ability to reduce SARS-CoV-2's RBD's affinity for ACE2 in a dose-dependent manner, and bind tightly to ACE2 without inhibiting its enzymatic activity. Gaussian accelerated molecular dynamics simulations (GaMD) further supported these findings, illustrating LOS's potential as a broad-spectrum antiviral agent against current and future coronavirus strains, meriting in vivo and clinical exploration.

Keywords: Bio-layer interferometry; COVID-19; GaMD; MD simulation; Spike protein; Sulfated carbohydrates.