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HTCC as a Polymeric Inhibitor of SARS-CoV-2 and MERS-CoV.
J Virol. 2021 01 28; 95(4)JV

Abstract

Among seven coronaviruses that infect humans, three (severe acute respiratory syndrome coronavirus [SARS-CoV], Middle East respiratory syndrome coronavirus [MERS-CoV], and the newly identified severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) are associated with a severe, life-threatening respiratory infection and multiorgan failure. We previously proposed that the cationically modified chitosan N-(2-hydroxypropyl)-3-trimethylammonium chitosan chloride (HTCC) is a potent inhibitor of human coronavirus NL63 (HCoV-NL63). Next, we demonstrated the broad-spectrum antiviral activity of the compound, as it inhibited all low-pathogenicity human coronaviruses (HCoV-NL63, HCoV-229E, HCoV-OC43, and HCoV-HKU1). Here, using in vitro and ex vivo models of human airway epithelia, we show that HTCC effectively blocks MERS-CoV and SARS-CoV-2 infection. We also confirmed the mechanism of action for these two viruses, showing that the polymer blocks the virus entry into the host cell by interaction with the S protein.IMPORTANCE The beginning of 2020 brought us information about the novel coronavirus emerging in China. Rapid research resulted in the characterization of the pathogen, which appeared to be a member of the SARS-like cluster, commonly seen in bats. Despite the global and local efforts, the virus escaped the health care measures and rapidly spread in China and later globally, officially causing a pandemic and global crisis in March 2020. At present, different scenarios are being written to contain the virus, but the development of novel anticoronavirals for all highly pathogenic coronaviruses remains the major challenge. Here, we describe the antiviral activity of an HTCC compound, previously developed by us, which may be used as a potential inhibitor of currently circulating highly pathogenic coronaviruses-SARS-CoV-2 and MERS-CoV.

Authors+Show Affiliations

Virogenetics Laboratory of Virology, Malopolska Centre of Biotechnology, Jagiellonian University, Krakow, Poland aleksandra.milewska@uj.edu.pl k.a.pyrc@uj.edu.pl. Microbiology Department, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland.NHC Key Lab of Enteric Pathogenic Microbiology, Jiangsu Provincial Centre for Disease Control & Prevention, Nanjing, Jiangsu, People's Republic of China.Virogenetics Laboratory of Virology, Malopolska Centre of Biotechnology, Jagiellonian University, Krakow, Poland. Microbiology Department, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland.Virogenetics Laboratory of Virology, Malopolska Centre of Biotechnology, Jagiellonian University, Krakow, Poland.Virogenetics Laboratory of Virology, Malopolska Centre of Biotechnology, Jagiellonian University, Krakow, Poland. Microbiology Department, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland.Virogenetics Laboratory of Virology, Malopolska Centre of Biotechnology, Jagiellonian University, Krakow, Poland. Microbiology Department, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland.Department of Physical Chemistry, Faculty of Chemistry, Jagiellonian University, Krakow, Poland.Nanjing Techboon Institute of Clinical Medicine, Nanjing, Jiangsu, People's Republic of China.Nanjing Techboon Institute of Clinical Medicine, Nanjing, Jiangsu, People's Republic of China.NHC Key Lab of Enteric Pathogenic Microbiology, Jiangsu Provincial Centre for Disease Control & Prevention, Nanjing, Jiangsu, People's Republic of China.NHC Key Lab of Enteric Pathogenic Microbiology, Jiangsu Provincial Centre for Disease Control & Prevention, Nanjing, Jiangsu, People's Republic of China.NHC Key Lab of Enteric Pathogenic Microbiology, Jiangsu Provincial Centre for Disease Control & Prevention, Nanjing, Jiangsu, People's Republic of China.NHC Key Lab of Enteric Pathogenic Microbiology, Jiangsu Provincial Centre for Disease Control & Prevention, Nanjing, Jiangsu, People's Republic of China.Department of Cardiac, Vascular and Endovascular Surgery and Transplantology, Silesian Centre for Heart Diseases, Medical University of Silesia in Katowice, Zabrze, Poland.Department of Cardiac, Vascular and Endovascular Surgery and Transplantology, Silesian Centre for Heart Diseases, Medical University of Silesia in Katowice, Zabrze, Poland.Department of Biomedical Chemistry, Faculty of Chemistry, University of Gdansk, Gdansk, Poland.NHC Key Lab of Enteric Pathogenic Microbiology, Jiangsu Provincial Centre for Disease Control & Prevention, Nanjing, Jiangsu, People's Republic of China. Centre for Global Health, Nanjing Medical University, Nanjing, Jiangsu, People's Republic of China.Department of Physical Chemistry, Faculty of Chemistry, Jagiellonian University, Krakow, Poland.Department of Physical Chemistry, Faculty of Chemistry, Jagiellonian University, Krakow, Poland.Virogenetics Laboratory of Virology, Malopolska Centre of Biotechnology, Jagiellonian University, Krakow, Poland aleksandra.milewska@uj.edu.pl k.a.pyrc@uj.edu.pl.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

33219167

Citation

Milewska, Aleksandra, et al. "HTCC as a Polymeric Inhibitor of SARS-CoV-2 and MERS-CoV." Journal of Virology, vol. 95, no. 4, 2021.
Milewska A, Chi Y, Szczepanski A, et al. HTCC as a Polymeric Inhibitor of SARS-CoV-2 and MERS-CoV. J Virol. 2021;95(4).
Milewska, A., Chi, Y., Szczepanski, A., Barreto-Duran, E., Dabrowska, A., Botwina, P., Obloza, M., Liu, K., Liu, D., Guo, X., Ge, Y., Li, J., Cui, L., Ochman, M., Urlik, M., Rodziewicz-Motowidlo, S., Zhu, F., Szczubialka, K., Nowakowska, M., & Pyrc, K. (2021). HTCC as a Polymeric Inhibitor of SARS-CoV-2 and MERS-CoV. Journal of Virology, 95(4). https://doi.org/10.1128/JVI.01622-20
Milewska A, et al. HTCC as a Polymeric Inhibitor of SARS-CoV-2 and MERS-CoV. J Virol. 2021 01 28;95(4) PubMed PMID: 33219167.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - HTCC as a Polymeric Inhibitor of SARS-CoV-2 and MERS-CoV. AU - Milewska,Aleksandra, AU - Chi,Ying, AU - Szczepanski,Artur, AU - Barreto-Duran,Emilia, AU - Dabrowska,Agnieszka, AU - Botwina,Pawel, AU - Obloza,Magdalena, AU - Liu,Kevin, AU - Liu,Dan, AU - Guo,Xiling, AU - Ge,Yiyue, AU - Li,Jingxin, AU - Cui,Lunbiao, AU - Ochman,Marek, AU - Urlik,Maciej, AU - Rodziewicz-Motowidlo,Sylwia, AU - Zhu,Fengcai, AU - Szczubialka,Krzysztof, AU - Nowakowska,Maria, AU - Pyrc,Krzysztof, Y1 - 2021/01/28/ PY - 2020/08/11/received PY - 2020/11/14/accepted PY - 2020/11/22/pubmed PY - 2020/11/22/medline PY - 2020/11/21/entrez KW - HTCC KW - MERS KW - SARS-CoV-2 KW - chitosan KW - coronaviridae KW - coronavirus KW - entry KW - inhibition KW - inhibitor JF - Journal of virology JO - J Virol VL - 95 IS - 4 N2 - Among seven coronaviruses that infect humans, three (severe acute respiratory syndrome coronavirus [SARS-CoV], Middle East respiratory syndrome coronavirus [MERS-CoV], and the newly identified severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) are associated with a severe, life-threatening respiratory infection and multiorgan failure. We previously proposed that the cationically modified chitosan N-(2-hydroxypropyl)-3-trimethylammonium chitosan chloride (HTCC) is a potent inhibitor of human coronavirus NL63 (HCoV-NL63). Next, we demonstrated the broad-spectrum antiviral activity of the compound, as it inhibited all low-pathogenicity human coronaviruses (HCoV-NL63, HCoV-229E, HCoV-OC43, and HCoV-HKU1). Here, using in vitro and ex vivo models of human airway epithelia, we show that HTCC effectively blocks MERS-CoV and SARS-CoV-2 infection. We also confirmed the mechanism of action for these two viruses, showing that the polymer blocks the virus entry into the host cell by interaction with the S protein.IMPORTANCE The beginning of 2020 brought us information about the novel coronavirus emerging in China. Rapid research resulted in the characterization of the pathogen, which appeared to be a member of the SARS-like cluster, commonly seen in bats. Despite the global and local efforts, the virus escaped the health care measures and rapidly spread in China and later globally, officially causing a pandemic and global crisis in March 2020. At present, different scenarios are being written to contain the virus, but the development of novel anticoronavirals for all highly pathogenic coronaviruses remains the major challenge. Here, we describe the antiviral activity of an HTCC compound, previously developed by us, which may be used as a potential inhibitor of currently circulating highly pathogenic coronaviruses-SARS-CoV-2 and MERS-CoV. SN - 1098-5514 UR - https://www.unboundmedicine.com/medline/citation/33219167/HTCC_as_a_Polymeric_Inhibitor_of_SARS_CoV_2_and_MERS_CoV_ L2 - http://jvi.asm.org/cgi/pmidlookup?view=long&pmid=33219167 DB - PRIME DP - Unbound Medicine ER -