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Updated: Mar 20, 2026

Early Viral Entry Assays for the Identification and Evaluation of Antiviral Compounds
Published on: October 29, 2015
HTCC: Broad Range Inhibitor of Coronavirus Entry
Aleksandra Milewska1,2, Kamil Kaminski3, Justyna Ciejka2
1Microbiology Department, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387 Krakow, Poland.
Insights
A novel chitosan derivative, HTCC, effectively inhibits common cold human coronaviruses by blocking viral entry. This discovery offers a potential new therapeutic strategy against these widespread respiratory pathogens.
Area of Science:
- Virology
- Materials Science
- Drug Discovery
Background:
- Six human coronaviruses (HCoVs) cause respiratory infections, with four (HCoV-NL63, HCoV-OC43, HCoV-229E, HCoV-HKU1) typically causing the common cold.
- Severe disease can occur in vulnerable populations, and no specific antiviral drugs currently exist for these common HCoVs, leaving only supportive care.
- Previous research identified N-(2-hydroxypropyl)-3-trimethylammonium chitosan chloride (HTCC) as a potential inhibitor of HCoV-NL63.
Purpose of the Study:
- To investigate the antiviral mechanism of HTCC against human coronaviruses.
- To evaluate the efficacy of HTCC and its derivatives against a broader range of low-pathogenic human coronaviruses.
Main Methods:
- In vitro assays to assess the inhibition of viral entry by HTCC.
- Testing of HTCC polymers with varying degrees of substitution against multiple low-pathogenic HCoV strains.
Main Results:
- HTCC was shown to inhibit the interaction between HCoV-NL63 and its cellular receptor, effectively blocking viral entry.
- HTCC polymers demonstrated inhibitory activity against all tested low-pathogenic human coronaviruses.
Conclusions:
- HTCC acts as a potent inhibitor of common cold human coronaviruses by preventing viral attachment and entry.
- Modified chitosan polymers represent a promising class of compounds for the development of novel antiviral therapies against prevalent HCoVs.
Abstract:
To date, six human coronaviruses have been known, all of which are associated with respiratory infections in humans. With the exception of the highly pathogenic SARS and MERS coronaviruses, human coronaviruses (HCoV-NL63, HCoV-OC43, HCoV-229E, and HCoV-HKU1) circulate worldwide and typically cause the common cold. In most cases, infection with these viruses does not lead to severe disease, although acute infections in infants, the elderly, and immunocompromised patients may progress to severe disease requiring hospitalization. Importantly, no drugs against human coronaviruses exist, and only supportive therapy is available. Previously, we proposed the cationically modified chitosan, N-(2-hydroxypropyl)-3-trimethylammonium chitosan chloride (HTCC), and its hydrophobically-modified derivative (HM-HTCC) as potent inhibitors of the coronavirus HCoV-NL63. Here, we show that HTCC inhibits interaction of a virus with its receptor and thus blocks the entry. Further, we demonstrate that HTCC polymers with different degrees of substitution act as effective inhibitors of all low-pathogenic human coronaviruses.
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