# Heparin Provides Antiviral Activity Against Rhinovirus-16 via an Heparan Sulfate Proteoglycan-Independent Mechanism

## TL;DR

Heparin can block HRV-16 infection in a way that does not involve heparan sulfate proteoglycans, suggesting a new antiviral strategy.

## Contribution

Heparin's antiviral effect against HRV-16 is shown to be independent of HSPG interactions, revealing a novel mechanism.

## Key findings

- Unfractionated heparin significantly reduces HRV-16 RNA expression in a dose- and time-dependent manner.
- Low-molecular-weight heparins are less effective at blocking HRV-16 infection compared to unfractionated heparin.
- The antiviral effect of heparin may be due to its size and high negative charge rather than HSPG interactions.

## Abstract

Human rhinovirus 16 (HRV-16) is a major cause of common colds and can exacerbate asthma and COPD, yet no approved antiviral treatments exist. Heparin, a highly sulfated polysaccharide, is known to block viral infection of many viruses that require attachment to heparan sulfate proteoglycans (HSPGs). Here, we investigated whether heparin inhibits HRV-16 infection. HRV-16 uses ICAM-1 as its attachment receptor and lacks a confirmed HSPG-binding mechanism. Notably, heparin inhibited HRV-16 infection in vitro in a dose- and time-dependent manner. Pre-treatment of either cells or virus particles with unfractionated heparin significantly reduced HRV-16 RNA expression at 24 and 48 h post-infection. In contrast, low-molecular-weight heparins blocked infection of HRV-16 significantly less effectively compared to unfractionated heparins. Our findings suggest that the inhibitory effect of unfractionated heparin on HRV-16 infection is likely independent of specific HSPGs interactions and may be mediated by the size and highly negative charge of unfractionated heparin. Importantly, the ability of unfractionated heparin to block viruses that do not require HSPGs for attachment implies a broader antiviral potential as a prophylactic or therapeutic agent against a variety of respiratory viruses.