The human coronavirus NL63 is generally classified as a common cold pathogen, though the infection may also result in severe lower respiratory tract diseases, especially in children, patients with underlying disease, and elderly. It has been previously shown that HCoV-NL63 is also one of the most important causes of croup in children. In the current manuscript we developed a set of polymer-based compounds showing prominent anticoronaviral activity. Polymers have been recently considered as promising alternatives to small molecule inhibitors, due to their intrinsic antimicrobial properties and ability to serve as matrices for antimicrobial compounds. Most of the antimicrobial polymers show antibacterial properties, while those with antiviral activity are much less frequent. A cationically modified chitosan derivative, N-(2-hydroxypropyl)-3-trimethylammonium chitosan chloride (HTCC), and hydrophobically-modified HTCC were shown to be potent inhibitors of HCoV-NL63 replication. Furthermore, both compounds showed prominent activity against murine hepatitis virus, suggesting broader anticoronaviral activity.
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http://dx.doi.org/10.1016/j.antiviral.2012.11.006 | DOI Listing |
Virology
January 2025
Department of Virology, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan. Electronic address:
Human coronaviruses (HCoVs) include common cold viruses such as HCoV-229E, OC43, NL63 and HKU1 as well as MERS-CoV and SARS-CoV, which cause severe respiratory disease. Recently, SARS-CoV-2 caused a COVID-19 pandemic. The nucleocapsid (N) protein of coronaviruses, which is essential for RNA binding and homodimerization, has a highly conserved structure across viruses.
View Article and Find Full Text PDFNat Commun
November 2024
Guangzhou National Laboratory, Guangzhou, 510005, China.
The RNA-dependent RNA polymerase (RdRp), 3C-like protease (3CL), and papain-like protease (PL) are pivotal components in the viral life cycle of SARS-CoV-2, presenting as promising therapeutic targets. Currently, all FDA-approved antiviral drugs against SARS-CoV-2 are RdRp or 3CL inhibitors. However, the mutations causing drug resistance have been observed in RdRp and 3CL from SARS-CoV-2, which makes it necessary to develop antivirals with novel mechanisms.
View Article and Find Full Text PDFAntiviral Res
December 2024
Arbutus Biopharma, Inc., Warminster, PA, USA.
Since the SARS-CoV-2 outbreak, there have been ongoing efforts to identify antiviral molecules with broad coronavirus activity to combat COVID-19. SARS-CoV-2's main protease (M) is responsible for processing the viral polypeptide into non-structural proteins essential for replication. Here, we present the biological characterization of AB-343, a covalent small-molecule inhibitor of SARS-CoV-2 M with potent activity in both cell-based (EC = 0.
View Article and Find Full Text PDFMicrobiol Spectr
November 2024
Aab Cardiovascular Research Institute, Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, New York, USA.
Unlabelled: Coronavirus disease 2019 (COVID-19) is caused by the infection of a coronavirus, named as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Coronaviruses can be replicated in the infected host cells. Coronavirus replication involves various steps, including membrane fusion, peri-nuclear particle formation, and matrix vesicle transport to the cell membrane the endoplasmic reticulum-Golgi-lysosome route.
View Article and Find Full Text PDFJ Virus Erad
September 2024
Department of Biology, University of Rome Tor Vergata, Rome, Italy.
Coronaviruses (CoV), zoonotic viruses periodically emerging worldwide, represent a constant potential threat to humans. To date, seven human coronaviruses (HCoV) have been identified: HCoV-229E, HCoV-NL63, HCoV-OC43 and HCoV-HKU1, globally circulating in the human population (seasonal coronaviruses, sHCoV), and three highly-pathogenic coronaviruses, SARS-CoV, MERS-CoV and SARS-CoV-2. Although sHCoV generally cause only mild respiratory diseases, severe complications may occur in specific populations, highlighting the need for broad-spectrum anti-coronavirus drugs.
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