Coronaviruses can spread rapidly to new host species and cause severe respiratory and enteric diseases in vertebrates, including humans. To date, seven coronaviruses have been identified in humans, with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) being the most notorious due to its substantial social and economic impact. Although anti-SARS-CoV-2 vaccines are available, infections remain widespread, highlighting the ongoing need for antiviral treatments. Here, we report the synthesis and evaluation of the activity of uridine glycoconjugates, designed as glycosyltransferase donor-type inhibitors incorporating a 1,2,3-triazole moiety. These compounds were tested against two model coronaviruses: murine hepatitis virus strain A59 (MHV) and human coronavirus strain NL63 (HCoV-NL63). Four of the synthesized compounds demonstrated strong antiviral activity against both viruses, and their efficacy was further confirmed against SARS-CoV-2. Our results suggest that these compounds interfere with the coronavirus infectivity and replication process. Thus, these novel compounds may prove to be effective broad-spectrum antiviral inhibitors.

Biotechnology Center Silesian University of Technology Krzywoustego 8 Gliwice 44 100 Poland

Department of Experimental Biology Faculty of Science Masaryk University Kamenice 735 Brno CZ 62500 Czech Republic

Department of Organic Chemistry Bioorganic Chemistry and Biotechnology Faculty of Chemistry Silesian University of Technology Krzywoustego 4 Gliwice 44 100 Poland

Laboratory of Emerging Viral Diseases Veterinary Research Institute Hudcova 70 Brno CZ 62100 Czech Republic

Laboratory of Emerging Viral Infections Veterinary Research Institute Hudcova 296 Brno CZ 62100 Czech Republic

Laboratory of Recombinant Vaccines Intercollegiate Faculty of Biotechnology University of Gdansk and Medical University of Gdansk Abrahama 58 Gdansk 80 307 Poland

Laboratory of Virus Molecular Biology Intercollegiate Faculty of Biotechnology University of Gdansk and Medical University of Gdansk Abrahama 58 Gdansk 80 307 Poland

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