Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Antiviral Efficacy of Heparan Sulfate and Enoxaparin Sodium against SARS-CoV-2: An In-Vitro/in-Silico Model

Virginia Fuochi
,
Salvatore Furnari
ORCID logo ,
Giuseppe Floresta
,
Vincenzo Patamia
ORCID logo ,
Chiara Zagni
ORCID logo ,
Filippo Drago
,
Antonio Rescifina
* ORCID logo ,
Pio Maria Furneri
* ORCID logo
Version 1 : Received: 20 October 2023 / Approved: 23 October 2023 / Online: 24 October 2023 (08:12:50 CEST)

How to cite: Fuochi, V.; Furnari, S.; Floresta, G.; Patamia, V.; Zagni, C.; Drago, F.; Rescifina, A.; Furneri, P.M. Antiviral Efficacy of Heparan Sulfate and Enoxaparin Sodium against SARS-CoV-2: An In-Vitro/in-Silico Model. Preprints 2023, 2023101486. https://doi.org/10.20944/preprints202310.1486.v1 Fuochi, V.; Furnari, S.; Floresta, G.; Patamia, V.; Zagni, C.; Drago, F.; Rescifina, A.; Furneri, P.M. Antiviral Efficacy of Heparan Sulfate and Enoxaparin Sodium against SARS-CoV-2: An In-Vitro/in-Silico Model. Preprints 2023, 2023101486. https://doi.org/10.20944/preprints202310.1486.v1

Abstract

SARS-CoV-2 attachment and entry inside mammalian cells is mainly mediated by human angiotensin-converting enzyme 2 (ACE2) and its interaction with spike protein. However, it is well known that spike protein also interacts with other molecules like glycosaminoglycans (GAG), e.g., heparan sulfate (HS) or Enoxaparin (EX), which are linear, anionically charged polysaccharides known for their biological activities. The mode of action of these two polysaccharides is to bind spike protein to block the interaction with ACE2 receptors. This study aimed to assess a model capable of confirming the activity of these GAGs in both the wild-type strain of SARS-CoV-2 and its variants, such as the highly variable BA.2.86. This was achieved by combining in silico modeling with in vitro determination using BacMam technology. The results showed the antiviral activity of HS and EX both in vitro and through the in-silico analysis, reconciling conflicting findings from recent studies on the cellular entry of SARS-CoV-2. In conclusion, it is possible to highlight the ability of these molecules to circumvent the high variability of SARS-CoV-2, providing valuable insights into intervention strategies targeting cell entry mechanisms and establishing a safe in vitro model.

Keywords

heparan sulfate; enoxaparin; coronavirus; SARS-CoV-2; ACE2, absorption inhibition; molecular docking

Subject

Medicine and Pharmacology, Epidemiology and Infectious Diseases

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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