Anticoronavirus Activity of Uridine Glycoconjugates Containing a 1,2,3-Triazole Moiety

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.