Caffeine:
Preliminary reports showed caffeine as a potential antiviral agent with its antiviral effect on certain viruses like the influenza virus, poliovirus, herpes simplex virus type 1 (HSV-1), and vaccinia virus (Yamazaki and Tagaya 1980). Subsequent studies showed that caffeine also inhibited viral RNA synthesis and viral protein synthesis in infected cells and thereby inhibiting growth and propagation of Newcastle disease virus (NDV), HSV-1, human immunodeficiency virus, vaccinia virus and polyomavirus (Olson and Consigli 1979; Shiraki and Rapp 1988; Dahl et al. 2005; Daniel et al. 2005). Caffeine was reported to inhibit the protein synthesis of HSV-1, which suppressed the formation of HSV-1 plaques by interfering with the cell-cell transmission of HSV-1 (Shiraki and Rapp 1988). Later it was further confirmed by the quantitative characterization that caffeine preferentially causes cytopathic effect (CPE) and the death of HSV-1 infected cells (Murayama et al. 2008). Therefore, such preferential CPE of caffeine on virally infected cells raises the potential of SARS-CoV-2 infected patient cells as caffeine could potentially reduce the viral load and also could induce selective death of virus-infected cells of COVID-19 patients. However, it is very important to note that caffeine-induced increased CPE and cell death was not detected for influenza virus and poliovirus and this was probably because these two viruses generally induced rapid cell death of infected cells immediately after infection and therefore masked the acceleration of caffeine-induced CPE of virus-infected cells if any (Murayama et al. 2008).
The aforementioned observation suggests that caffeine-induced selective degeneration of virally infected cells may be dependent on the species of the virus. In a more recent meta-analysis on the effect of caffeine in patients with chronic hepatitis C, it was shown that patients with higher caffeine intake showed 61% reduced risk of developing advanced hepatic fibrosis and was also associated with lower serum ALT levels in chronic hepatitis C patients compared to lower caffeine intake patient group (Jaruvongvanich et al. 2017). Specifically for hepatitis C, an in-vitro study also demonstrated that caffeine efficiently inhibited the replication of hepatitis C replication in a dose-dependent manner, further confirming the antiviral potential of caffeine (Batista et al. 2015). Overall, there is compelling evidence for the broad-spectrum antiviral role of caffeine, and its antiviral actions are well characterized in several viral species, and it could play a critical role in being a potential antiviral therapy in COVID-19 patients as well