Supplementary Table 8. Current studies investigating COVID-19/ other coronavirus strains and Tacrolimus.

Study Ref	Title	Authors	Country of study	Year	Summary of results
[81]	Replication of human coronaviruses SARS-CoV, HCoV-NL63 and HCoV-229E is inhibited by the drug FK506	Carbajo-Lozoya et al.	Germany/Switzerland	2012	Coronaviruses represent the group of RNA viruses with the largest RNA genome to date therefore the development of resistant mutants to targeted drugs remains a concern. Viral replication represents potential antiviral targets. Study performed genome-wide SARS-CoV yeast-two-hybrid interaction screen with human cDNA libraries identifying FK506-binding proteins as interaction partners of SARS-CoV non-structural protein 1 (Nsp1). FK506-binding proteins bind the immunosuppressive drug FK506 (tacrolimus). Since Nsp1 interacts with FK506-binding proteins, investigated whether FK506 inhibits replication of human coronaviruses. VeroFM cells infected with SARS-CoV and other human coronaviruses and treated with FK506. Study found that FK506 inhibits the replication of SARS-CoV, HCoV-NL63 and HCoV-229E at non-toxic, low-micromolar concentrations with reduction in viral titers to undetectable levels. All human coronaviruses sensitive to FK506 indicating the involvement of FK506-binding proteins in viral replication.
[82]	MERS CoV infection in two renal transplant recipients: Case report	Al Ghamdi et al	Saudi Arabia	2015	Pneumonia caused by MERS-CoV associated with severe morbidity and mortality in immunocompromised patients. Data on clinical picture in solid organ transplant recipients and effect of anti-rejection immunosuppressive regimens unclear. 30-year old patient with renal transplant on immunosuppressive regimen of tacrolimus. Tested positive for MERS CoV through nasopharyngeal swab. Received antibacterial therapy and mycophenolate mofetil dose reduced and underwent full recovery. Difficult to pinpoint why made full recovery compared to other case study (not on tacrolimus) who died.
[83]	Human coronavirus NL63 replication is cyclophilin A-dependent and inhibited by non-immunosuppressive cyclosporine A-derivatives including Alisporivir	Carbajo-Lozoya et al	Germany	2014	Previous study shown that FK506 inhibit coronavirus replication. This study further shows that novel non-immunosuppressive derivatives of CsA and FK506 strongly inhibit the growth of human coronavirus HCoV-NL63 at low-micromolar, non-cytotoxic concentrations in cell culture. HCoV-NL63 and HCoV-HKU1 discovered in 2004 and 2005 causing more severe lower respiratory tract infections in younger children. PPIase-independent activities of CsA and FK506 exerted by gain-of-function, result from binary complexes formed by binding of the drugs to FKBPs. Based on inhibition of the protein phosphatase activity of calcineurin, these complexes block the cellular calcineurin/NFAT pathway thereby interfering with T-cell activation and IL-2 production. FK506 analogues (altered by side chain modification)