tetano
Editor, Senior Moderator
Virol J
. 2024 Jan 25;21(1):29.
doi: 10.1186/s12985-024-02299-w. Quercetin inhibits SARS-CoV-2 infection and prevents syncytium formation by cells co-expressing the viral spike protein and human ACE2
Annie V Roy[SUP] 1 [/SUP], Michael Chan[SUP] 2 [/SUP], Logan Banadyga[SUP] 2 3 [/SUP], Shihua He[SUP] 2 [/SUP], Wenjun Zhu[SUP] 2 4 [/SUP], Michel Chrétien[SUP] 1 [/SUP], Majambu Mbikay[SUP] 5 [/SUP]
Affiliations
Background: Several in silico studies have determined that quercetin, a plant flavonol, could bind with strong affinity and low free energy to SARS-CoV-2 proteins involved in viral entry and replication, suggesting it could block infection of human cells by the virus. In the present study, we examined the ex vivo ability of quercetin to inhibit of SARS-CoV-2 replication and explored the mechanisms of this inhibition.
Methods: Green monkey kidney Vero E6 cells and in human colon carcinoma Caco-2 cells were infected with SARS-CoV-2 and incubated in presence of quercetin; the amount of replicated viral RNA was measured in spent media by RT-qPCR. Since the formation of syncytia is a mechanism of SARS-CoV-2 propagation, a syncytialization model was set up using human embryonic kidney HEK293 co-expressing SARS-CoV-2 Spike (S) protein and human angiotensin converting enzyme 2 (ACE2), [HEK293(S + ACE2) cells], to assess the effect of quercetin on this cytopathic event by microscopic imaging and protein immunoblotting.
Results: Quercetin inhibited SARS-CoV-2 replication in Vero E6 cells and Caco-2 cells in a concentration-dependent manner with a half inhibitory concentration (IC[SUB]50[/SUB]) of 166.6 and 145.2 µM, respectively. It also inhibited syncytialization of HEK293(S + ACE2) cells with an IC[SUB]50[/SUB] of 156.7 µM. Spike and ACE2 co-expression was associated with decreased expression, increased proteolytic processing of the S protein, and diminished production of the fusogenic S2' fragment of S. Furin, a proposed protease for this processing, was inhibited by quercetin in vitro with an IC[SUB]50[/SUB] of 116 µM.
Conclusion: These findings suggest that at low 3-digit micromolar concentrations of quercetin could impair SARS-CoV-2 infection of human cells partly by blocking the fusion process that promotes its propagation.
Keywords: HEK293 cells; Human ACE2; Quercetin; SARS-CoV-2; Spike protein; Syncytium formation.
. 2024 Jan 25;21(1):29.
doi: 10.1186/s12985-024-02299-w. Quercetin inhibits SARS-CoV-2 infection and prevents syncytium formation by cells co-expressing the viral spike protein and human ACE2
Annie V Roy[SUP] 1 [/SUP], Michael Chan[SUP] 2 [/SUP], Logan Banadyga[SUP] 2 3 [/SUP], Shihua He[SUP] 2 [/SUP], Wenjun Zhu[SUP] 2 4 [/SUP], Michel Chrétien[SUP] 1 [/SUP], Majambu Mbikay[SUP] 5 [/SUP]
Affiliations
- PMID: 38273400
- PMCID: PMC10811921
- DOI: 10.1186/s12985-024-02299-w
Background: Several in silico studies have determined that quercetin, a plant flavonol, could bind with strong affinity and low free energy to SARS-CoV-2 proteins involved in viral entry and replication, suggesting it could block infection of human cells by the virus. In the present study, we examined the ex vivo ability of quercetin to inhibit of SARS-CoV-2 replication and explored the mechanisms of this inhibition.
Methods: Green monkey kidney Vero E6 cells and in human colon carcinoma Caco-2 cells were infected with SARS-CoV-2 and incubated in presence of quercetin; the amount of replicated viral RNA was measured in spent media by RT-qPCR. Since the formation of syncytia is a mechanism of SARS-CoV-2 propagation, a syncytialization model was set up using human embryonic kidney HEK293 co-expressing SARS-CoV-2 Spike (S) protein and human angiotensin converting enzyme 2 (ACE2), [HEK293(S + ACE2) cells], to assess the effect of quercetin on this cytopathic event by microscopic imaging and protein immunoblotting.
Results: Quercetin inhibited SARS-CoV-2 replication in Vero E6 cells and Caco-2 cells in a concentration-dependent manner with a half inhibitory concentration (IC[SUB]50[/SUB]) of 166.6 and 145.2 µM, respectively. It also inhibited syncytialization of HEK293(S + ACE2) cells with an IC[SUB]50[/SUB] of 156.7 µM. Spike and ACE2 co-expression was associated with decreased expression, increased proteolytic processing of the S protein, and diminished production of the fusogenic S2' fragment of S. Furin, a proposed protease for this processing, was inhibited by quercetin in vitro with an IC[SUB]50[/SUB] of 116 µM.
Conclusion: These findings suggest that at low 3-digit micromolar concentrations of quercetin could impair SARS-CoV-2 infection of human cells partly by blocking the fusion process that promotes its propagation.
Keywords: HEK293 cells; Human ACE2; Quercetin; SARS-CoV-2; Spike protein; Syncytium formation.