Supplementary Table 7. Current studies investigating COVID-19/ other coronavirus strains and Mycophenolate.
| Study Ref | Title | Authors | Country of study | Year | Summary of results |
|---|---|---|---|---|---|
| [68] | Interferon-β and mycophenolic acid are potent inhibitors of middle east respiratory syndrome coronavirus in cell-based assays | Hart et al | USA | 2014 | (In vitro only) MPA showed strong inhibition, with an IC50 of 2.87 mM. This drug may provide an alternative to ribavirin for treatment of MERS-CoV. In conclusion, IFN-b, MPA or a combination of the two may be beneficial in the treatment of MERS-CoV or as a post-exposure intervention in high-risk patients with known exposures to MERS-CoV. |
| [69] | Disulfiram can inhibit MERS and SARS coronavirus papain-like proteases via different modes | Lin et al | Taiwan | 2018 | (In vitro) Note. (PLpros)= Papain-like proteases MERS-CoV and SARS-CoV – act as a potential anti-viral target for drugs Multiple inhibition assays also support a kinetic mechanism by which disulfiram together with 6TG and/or MPA can synergistically inhibit MERS-CoV PLpro, but not, due to its competitive mode of inhibition, SARS-CoV PLpro. Synergistic inhibition of MERS-CoV PLpro by disulfiram and 6-thioguanine or mycophenolic acid implies the potential for combination treatments using these three clinically available drugs. |
| [70] | Thiopurine analogs and mycophenolic acid synergistically inhibit the papain-like protease of Middle East respiratory syndrome coronavirus | Cheng et al | Taiwan | 2015 | (In vitro) At the time of the study, there were no potent inhibitors that target MERS-CoV PLpro. The authors report that the immunosuppressive drug mycophenolic acid, was able to inhibit MERS-CoV PLpro. MPA is a non-competitive inhibitor of MERS-CoV PLpro. |
| [71] | Broad-spectrum antivirals for the emerging Middle East respiratory syndrome coronavirus | Chan et al | Hong Kong/China | 2013 | (In vitro) The authors assessed the anti-MERS-CoV activities of several compounds. Only mycophenolic acid exhibited low EC50 and high selectivity index. They found that a combination of mycophenolic acid and IFN-b1b lowered the EC50 of each drug by 1-3 times. Mycophenolic acid exhibits a number of attributes that support its practical use in MERS-CoV infection. It is commonly available in two forms, the prodrug mycophenolate mofetil and the salt mycophenolate sodium, and could be given orally. Interferon-b1b with mycophenolic acid should be considered in treatment trials of MERS. |
| [72] | High-Throughput Screening and Identification of Potent Broad-Spectrum Inhibitors of Coronaviruses. | Shen et al | China | 2019 |
(In vitro) The authors sought to identify potent broad-spectrum inhibitors of corona viruses. They concluded that they had identified seven compounds (lycorine, emetine, monensin sodium, mycophenolate mofetil, mycophenolic acid, phenazopyridine, and pyrvinium pamoate) as broad-spectrum inhibitors according to their strong inhibition of replication by four CoVs in vitro at low-micromolar concentrations. They all inhibited the replication of all CoVs with EC50 values of 5μm. Mycophenolate mofetil and mycophenolic acid, showed a similar antiviral effect on the four CoVs suggesting that the two drugs might harbour similar core structures and antiviral mechanisms. In vivo antiviral activity is unknown from this study. |
| [73] | Glycyrrhizin, an active component of liquorice roots, and replication of SARS-associated coronavirus | Cinatl et al | Germany | 2003 | (In vitro but using clinical samples - Abstract only) The authors assessed the antiviral activities of ribavirin, 6-azauridine, pyrazofurin, mycophenolic acid, and glycyrrhizin against two clinical isolates of coronavirus (FFM-1 and FFM-2) from patients with SARS admitted to the clinical centre of Frankfurt University, Germany. Mycophenolic acid did not affect replication of the SARS-associated coronaviruses. |
| [74] | Treatment outcomes for patients with Middle Eastern Respiratory Syndrome Coronavirus (MERS CoV) infection at a coronavirus referral center in the Kingdom of Saudi Arabia. | Al Ghamdi et al | Saudi Arabia | 2016 | (Clinical example) Eight patients (15.7%) received mycophenolate mofetil, seven of these patients received it in combination with interferon beta. All patients who received mycophenolate mofetil survived. The authors concluded that whilst treatment with beta interferon and mycophenolate mofetil predicted survival (in univariate analysis only), the greatest predictor of survival was the severity of illness on presentation. |
| [75] | Treatment with lopinavir/ritonavir or interferon-beta1b improves outcome of MERSCoV infection in a nonhuman primate model of common marmoset | Chan et al | Hong Kong/China | 2015 | (In vivo) The authors assessed 3 repurposed drugs with potent in vitro anti-MERS-CoV activity (mycophenolate mofetil, lopinavir/ritonavir, and interferon-β1b) in common marmosets with severe disease resembling MERS in humans. all MMF-treated animals developed severe and/or fatal disease with higher mean viral loads. The authors concluded that MMF alone may worsen MERS and should not be used. |
| [76] | Enhancement of the infectivity of SARS-CoV in BALB/c mice by IMP dehydrogenase inhibitors, including ribavirin | Barnard et al | USA | 2006 | In vivo study in BALB/c mice (a replication model for SARS infections) In mycophenolic acid-treated mice, the lung virus titers (aka viral load) increased with increasing dosage, although these increases in lung virus titers were not quite significantly different from the lung virus titers in placebo-treated, infected mice. |
| [77] | A review of treatment modalities for Middle East Respiratory Syndrome | Mo and Fisher | Singapore | 2016 | (Review) Mycophenolic acid also inhibits purine nucleotide synthesis in lymphocytes. This makes it a popular immunosuppressant in solid-organ transplants and autoimmune diseases such as systemic lupus erythematosus. The use of mycophenolic acid monotherapy has not been reported in MERS. IFN-b and mycophenolic acid combination therapy was described in a retrospective observational study in Saudi Arabia involving 51 patients; all of the 8 patients who received IFN-b and mycophenolic acid survived. Corticosteroids, ribavirin monotherapy and mycophenolic acid are likely to cause more harm than benefit. There are no clinical data on the efficacy of mycophenolic acid in SARS or MERS. However, it led to severe and/or fatal disease with higher mean viral loads in an animal model. |
| [78] | Update on therapeutic options for Middle East Respiratory Syndrome Coronavirus (MERS-CoV) | Al-Tawfiq and Memish | Saudi Arabia | 2017 | (Review) MPA mechanism of action - Direct and indirect antiviral activity by modulation of IFN response The use of mycophenolate in the common marmoset animal model resulted in higher mortality than untreated animals: Mortality rate was 67% (untreated and MMF treated) at 36 h post inoculation versus 0%–33% (lopinavir/ ritonavir-treated and interferon-β1b- treated |
| [79] | Middle East Respiratory syndrome coronavirus: Another zoonotic betacoronavirus causing SARS-like disease | Chan et al | Hong Kong/China | 2015 | (Review) The combination of mycophenolic acid and interferon beta 1b shows synergistic activity against MERS-CoV in Vero cells. The desirable pharmacokinetics of mycophenolic acid compared to ribavirin warrants further evaluation, although the potential inhibitory effect on the immune system and therefore neutralising antibody production should be fully assessed in animal models before use in humans. A fatal case of MERS was reported in a renal transplant recipient who was receiving antirejection therapy consisting of prednisone, mycophenolate mofetil, and cyclosporine, but the dosage, serum drug level of mycophenolate mofetil, and resulting lymphocyte count were not reported |
| [80] | A review of candidate therapies for Middle East respiratory syndrome from a molecular perspective. | Rabaan et al | Saudi Arabia | 2017 | (Review) Reiteration of the promising results of MPA in an in vitro setting, however, the marmoset animal model resulted in fatal disease and high viral loads. The authors therefore state that MPA should be used with caution for treatment of MERS-CoV. |
The EC50 is the concentration of a drug that gives half-maximal response. The IC50 is the concentration of an inhibitor where the response (or binding) is reduced by half. These terms are referred to a few times within the summary table.