In a recent study published in the journal Cell and biologyScientists investigated whether coffee has an (inhibiting) effect on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
Several SARS-CoV-2 variants have emerged during the coronavirus disease 2019 (COVID-19) pandemic. In addition, vaccine protection wanes over time, prompting the introduction of booster doses. In addition, diet may affect the efficacy of SARS-CoV-2 infection. Recent reports suggest that a diet luxurious in polyphenols and physical activity may induce an busy immune response and reduce the risk of severe disease.
Coffee is one of the most commonly consumed beverages and contains polyphenols such as caffeic acid and chlorogenic acid (CGA), as well as antioxidants such as trigonelline, melanoidins, and cafestol. One study found that coffee consumption (at least one cup per day) was associated with a 10% lower risk of COVID-19 among participants in the United Kingdom (UK) Biobank. However, the underlying mechanisms remain unclear.
Test: Coffee as a Dietary Strategy to Prevent SARS-CoV-2 Infection
About the study
In this study, researchers investigated the efficacy of coffee against SARS-CoV-2. They used a SARS-CoV-2 pseudovirus assay to assess the effect of coffee on viral entry into a human embryonic kidney cell line (293T) expressing angiotensin-converting enzyme 2 (ACE2). Ground coffee (6 mg/ml) showed a dose-dependent reduction in viral entry. They then tested the effect of several commercial instant coffee products.
Instant coffee products (1 mg/ml) consistently inhibited the entry of wild-type SARS-CoV-2 and variants (Alpha, Delta, and Omicron). The team then assessed how coffee additives, such as cream, skim milk, and sugar, affected its potency. This showed that the additives had no effect on the inhibitory effects of coffee. The researchers conducted an enzyme-linked immunosorbent assay (ELISA) and observed that ground and instant coffee disrupted spike-ACE2 interactions.
In addition, the team observed that ground and instant coffee inhibited the activity of transmembrane serine protease 2 (TMPRSS2). They then tested whether the expression of ACE2 and TMPRSS2 could be regulated. To do this, HepG2 hepatocellular carcinoma (HCC) cells and Huh7 cells, which express high levels of ACE2 and TMPRSS2, respectively, were treated with different concentrations of coffee. This significantly reduced the levels of ACE2 and TMPRSS2 transcript and protein.
The sixth (F6) and seventh (F7) fractions showed sturdy inhibitory effects on SARS-CoV-2 entry. CGA and caffeine were detected in F6, whereas luteolin, methylferulic acid, isochlorogenic acid A (isoCGA-A), isoCGA-B, and isoCGA-C were present in F7. Subsequently, the inhibitory effect of the mixture containing five F7 compounds was only half of that observed for F7, suggesting that some undetected compounds in fraction F7 contributed to the inhibition.
In addition, the compounds detected in F6 and F7 were tested separately. IsoCGA, CGA, and caffeine inhibited the entry of wild-type SARS-CoV-2, and isoCGA-A was the most potent compound. Luteolin and methylferulic acid did not show any inhibitory effect. In addition, isoCGA, especially isoCGA-A, effectively inhibited the entry of the Alpha, Delta, and Omicron variants. Further analysis indicated that isoCGA and CGA could inhibit the interaction between ACE2 and the viral spike.
IsoCGA were the best candidates in docking analyses based on binding energy scores, followed by CGA and caffeine. Next, we evaluated the effects of isoCGA, CGA, and caffeine on TMPRSS2 activity. IsoCGA achieved consistently better TMPRSS2 inhibition than CGA or caffeine. Furthermore, decaffeinated coffee was found to reduce spike-ACE2 interactions and TMPRSS2 activity.
Finally, 64 well Taiwanese subjects aged 21–40 years were randomly assigned to consume regular coffee (high or low dose), decaffeinated coffee (high or low dose), or water (control group) for 2 days. Sera were collected before and after the intervention. Samples from most individuals in the regular coffee groups inhibited wild-type SARS-CoV-2 and the Omicron variant. Similarly, sera from decaffeinated coffee consumers, especially the high-dose group, also inhibited SARS-CoV-2.
Conclusions
The results suggest that coffee may limit SARS-CoV-2 infection by inhibiting spike-ACE2, TMPRSS2, and CTSL interactions. Coffee also reduced ACE2 and TMPRSS2 protein levels. Bioactive compounds in coffee, such as CGA, isoCGA, and caffeine, showed inhibitory effects. A human study showed that sera from regular and decaffeinated coffee consumers can inhibit SARS-CoV-2, including the Omicron variant. Overall, the authors suggest that coffee consumption may be a potential dietary strategy to prevent infections in the post-COVID era.
