HTCC as a Polymeric Inhibitor of SARS-CoV-2 and MERS-CoV

• Published in: Journal of virology 2021-01, Vol.95 (4)
• Main Authors: Milewska, Aleksandra, Chi, Ying, Szczepanski, Artur, Barreto-Duran, Emilia, Dabrowska, Agnieszka, Botwina, Pawel, Obloza, Magdalena, Liu, Kevin, Liu, Dan, Guo, Xiling, Ge, Yiyue, Li, Jingxin, Cui, Lunbiao, Ochman, Marek, Urlik, Maciej, Rodziewicz-Motowidlo, Sylwia, Zhu, Fengcai, Szczubialka, Krzysztof, Nowakowska, Maria, Pyrc, Krzysztof
• Format: Article
• Language: English
• Subjects: Antiviral Agents - pharmacology; Chitosan - analogs & derivatives; Chitosan - pharmacology; Coronavirus Infections - drug therapy; Coronavirus Infections - metabolism; Coronavirus Infections - virology; COVID-19 - drug therapy; COVID-19 - epidemiology; COVID-19 - virology; Humans; Middle East Respiratory Syndrome Coronavirus - drug effects; Middle East Respiratory Syndrome Coronavirus - metabolism; Middle East Respiratory Syndrome Coronavirus - physiology; Pandemics; Quaternary Ammonium Compounds - pharmacology; Respiratory Mucosa - drug effects; Respiratory Mucosa - virology; SARS-CoV-2 - drug effects; SARS-CoV-2 - metabolism; SARS-CoV-2 - physiology; Spike Glycoprotein, Coronavirus - antagonists & inhibitors; Spike Glycoprotein, Coronavirus - metabolism; Vaccines and Antiviral Agents; Virus Internalization - drug effects
• ISSN: 0022-538X; 1098-5514
• DOI: 10.1128/jvi.01622-20

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 and 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. 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.