Anti-SARS-CoV-2 agent (Univ. Bordeaux)

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.

The design and synthesis of novel bis[(substituted-aminomethyl)phenyl]phenyl pyrrolopyrimidines, pyrrolopyridines, pyrazolopyrimidines, imidazopyrimidines, and tris[(substituted-aminomethyl)phenyl]phenyl pyrrolopyrimidines are reported here. These original G-quadruplex (G4) ligands have been then subjected to a screening on SARS-CoV-2 using a competition HTRF assay by targeting the SUD-NM/TRF2 RNA G4 interaction. The more promising derivatives have been evaluated in vitro to determine their potential antiviral effect on two different cell lines infected by two SARS-CoV-2 strains. This study revealed a clear correlation between their antiviral property and their efficacy to prevent the SUD/G4 interaction. This correlation supports the choice of SUD/RNA G4 complexes formed during SARS-CoV-2 infection as new antiviral targets.