Table 1.
Approved nucleos(t)ide-based antiviral and antineoplastic drugs with multi-target activity.
| Name | Type | Approved antiviral drug (approval date) | Approved antineoplastic drug (approval date) | Active clinical-stage developmenta | Experimental development |
|---|---|---|---|---|---|
| Acyclovir | Acyclic guanosine analogue | HSV, VZV (1982) | Breast cancer (Shaimerdenova et al., 2017) EBV (Pagano et al., 2018) |
||
| Azacitidine | Cytidine analogue | Myelodysplastic syndrome (2004) | AdV (Alexeeva et al. (2001); (Alexeeva et al., 2015) HMPV (Bösl et al., 2019) HIV-1 (Dapp et al., 2009; Rawson et al., 2016a) HIV-1 – synergy in combination with resveratrol (Rawson et al., 2016b) HIV-2 (Beach et al., 2014) RVFV (Ianevski et al., 2018) HTLV-1 (Diamantopoulos et al., 2012) HSV-1, FLUAV (Ianevski et al., 2018) |
||
| Brivudine | Thymidine analogue | HSV-1, VZV (2002)b | |||
| Clofarabine | Adenosine analogue | Acute lymphoblastic leukaemia (2004) | HIV-1 (Daly et al., 2016) HIV-1, HIV-2 (Beach et al., 2014) |
||
| Decitabine | Cytidine analogue | Myelodysplastic syndrome (2006) | HIV-1 (Clouser et al., 2010) HIV-1 – synergy in combination with gemcitabine (Clouser et al., 2010) HIV-1 – synergy in combination with resveratrol (Jonathan M.O. Rawson et al., 2016b) MuLV (Clouser et al., 2012) |
||
| Famciclovir | Acyclic guanosine analogue | HSV, VZV (1994) | |||
| Galidesivir | Adenosine analogue | EBOV (n/a) | MARV (phase 1, NCT03800173) YFV (phase 1, NCT03891420) |
ZIKV (Julander et al., 2017) broad-spectrum antivirals (Westover et al., 2018) | |
| Ganciclovir | Acyclic guanosine analogue | HSV, VZV, CMV (1989) | EBV (Pagano et al., 2018) | ||
| Gemcitabine | Cytidine analogue | Various carcinomas (1995): non-small cell lung cancer, pancreatic cancer, bladder cancer breast cancer ovarian cancer | HIV-1 (Rawson et al. (2013); Clouser et al. (2010); (Clouser et al., 2012) HIV-1 – synergy in combination with decitabine (Clouser et al., 2010) MuLV (Clouser et al., 2012) HIV-2 (Beach et al., 2014) ZIKV (Kuivanen et al., 2017) Enteroviruses including poliovirus (Kang et al., 2015; Zhang et al., 2017) Enteroviruses – synergy with ribavirin (Kang et al., 2015) Rhinoviruses (Song et al., 2017) HCV (Beran et al., 2012) Coronaviruses (Dyall et al., 2014) SINV, HSV-1, FLUAV (Denisova et al., 2012) Gram-positive bacteria (Jordheim et al., 2012; Sandrini et al., 2007; Thomson and Lamont, 2019) |
||
| Lamivudine | L-Cytidine analogue | HIV (1999) HBV (1995) |
|||
| Penciclovir | Acyclic guanosine analogue | HSV, VZV (1996) | |||
| Ribavirin | Nucleoside analogue | RSV, HCV (1985) viral haemorrhagic fevers | HBV (phase 3, (NCT03759782, in combination with tenofovir) | Enteroviruses (Bauer et al., 2017) Influenza virus (Pauly and Lauring, 2015) |
|
| Sofosbuvir | Uridine nucleotide analogue | HCV (2013) | HBV (phase 2, NCT03312023; I combination with ledipasvir) | DENV (Xu et al., 2017) YFV (De Freitas et al., 2019) ZIKV (Mesci et al., 2018; Bullard-Feibelman et al., 2017) CHIKV (Ferreira et al., 2019) |
|
| Telbivudine | L-Thymidine | HBV (2006) | Immunomodulatory, anti-inflammatory properties (Van Linthout et al., 2018) | ||
| Tenofovir disoproxil | Acyclic adenosine nucleotide analogue | HIV (2001) HBV (2008) |
|||
| Tenofovir alafenamide | Acyclic adenosine nucleotide analogue | HBV (2016) HIV (several combination, see Table 2) |
HBV (phase 2, NCT03434353, in combination with inarigivir) | ||
| Trifluridine | Thymidine analogue | HSV (1980) | Metastatic colorectal cancer (2015) in combination with tipiracil | Mycoplasma pneumonia (Sun and Wang, 2013) | |
| Valaciclovir | Acyclic guanosine analogue | HSV, VZV, CMV (1995) | |||
| Valganciclovir | Acyclic guanosine analogue | HSV, VZV, CMV (2001) | EBV (Pagano et al., 2018) | ||
| Vidarabine | Arabinosyl adenine analogue | HSV, VZV (1976) |
a
Clinical data from ClinicalTrials.gov (see https://www.clinicaltrials.gov/) in July 2019.
b
Approved by European Medicines Agency (EMA).