Table 2.
Summary of potential MERS-CoV therapies and vaccines.
| Therapeutic target | Type of therapy | Therapy/ Vaccine name |
Study type | Advantages | Disadvantages | Reference |
|---|---|---|---|---|---|---|
| S1/DPP4 binding | Antibody (mouse): S1 RBD | Mersmab | In vitro | (Du et al., 2014) | ||
| Antibody (human): S1 RBD |
m336, m337, m338 |
In vitro In vivo (Mouse, rabbit- m336) |
(Agrawal et al., 2016, Houser et al., 2016, Ying et al., 2014) | |||
| Antibody (human): S1 RBD |
MERS-4, MERS-27 | In vitro | (Jiang et al., 2014, Yu et al., 2015) | |||
| Antibody (mouse- humanized): S1 RBD | 4C2 |
In vitro In vivo (Mouse) |
Prophylactic and therapeutic | (Li et al., 2015) | ||
| Antibody (mouse- humanized): S1 RBD | hMS-1 |
In vitro In vivo (Mouse) |
(Qiu et al., 2016) | |||
| Antibody (human): S1 RBD |
LCA60 |
In vitro In vivo (Mouse) |
Targets both NTD and RBD; stable CHO cell line; prophylactic and therapeutic | (Corti et al., 2016) | ||
| Antibody (human): S1 RBD |
3B11-N |
In vitro In vivo (rhesus monkeys) |
Prophylactic | (Johnson et al., 2016) | ||
| Antibody (human): S1 RBD |
MERS-GD27 MERS-GD33 |
In vitro | Synergistic effect; Different epitopes; MERS-GD27 overlaps receptor binding site | (Niu et al., 2018) | ||
| Antibody (human- anti-DPP4) |
2F9, 1F7, YS110 | In vitro | (Ohnuma et al., 2013) | |||
| RBD-IgG fusion vaccine candidate | RBD s377–588- Fc IgG fusion |
In vitro In vivo (Mouse) |
Humoral response in mice; potential intranasal administration; improved by adjuvant; divergent strains/ escape mutants; CHO cell line |
(Du et al., 2013, Ma et al., 2014, Nyon et al., 2018, Tai et al., 2017, Zhang et al., 2015, Zhang et al., 2016b) | ||
| Nanoparticles vehicle (vaccine candidate) | Full-length S protein proprietary nanoparticles |
In vitro In vivo (Mouse) |
Use of adjuvants improves humoral response | Stable expression of abundant full-length S protein difficult | (Coleman et al., 2014) | |
| Nanoparticles and virus vehicle (vaccine candidate) | Full-length S protein: Ad5/MERS and S protein nanoparticles | Heterologous prime-boost: | In vivo (Mouse) | T cell and neutralizing antibody responses; potentially prophylactic | (Jung et al., 2018) | |
| Virus vehicle (vaccine candidate) | MVA expressing full-length S protein | MVA-MERS-S |
In vitro In vivo (Mouse, camel) |
T cell and neutralizing antibody responses; entering human clinical trials; potential for veterinary use- | (Langenmayer et al., 2018, Volz et al., 2015) | |
| ad5 or ad41 adenovirus expressing full-length S |
In vitro In vivo (Mouse) |
T cell and neutralizing antibody responses | (Guo et al., 2015) | |||
| Measles virus expressing full-length S |
In vitro In vivo (Mouse) |
T cell and neutralizing antibody responses | (Malczyk et al., 2015) | |||
| Chimeric vesicular stomatitis virus (VSV) expressing full-length S |
In vitro In vivo (Rhesus monkeys) |
T cell and neutralizing antibody responses | (Liu et al., 2018) | |||
| Chimpanzee adenovirus (ChAdOx1) expressing full-length S |
In vitro In vivo (mouse) |
T cell and neutralizing antibody responses; entering human clinical trials; potential for veterinary use | (Alharbi et al., 2017) | |||
| Plasmid vaccine | GLS-5300 |
In vitro In vivo (Mouse, camels, and macaques) Human clinical trials |
T cell and neutralizing antibody responses; in phase I clinical trial | (Inovio, 2016, Muthumani et al., 2015) | ||
| Viral S2-host membrane fusion | Anti-HR2 viral peptide | HR2P | In vitro | (Lu et al., 2014b) | ||
| Anti-HR2 viral peptide | HR2P-M2 |
In vitro In vivo (Mouse) |
Blocks 6HB bundle formation; enhances IFN-β effect; potential intranasal treatments | (Bosch et al., 2004, Channappanavar et al., 2015, Liu et al., 2004) | ||
| Three HR1 and two HR2 protein | MERS-5HB | In vitro | Inhibits fusion and entry | (Sun et al., 2017) | ||
| Immune evasion response | IFN-α2b and ribavirin |
In vitro In vivo (Macaque) |
Combination therapy- reduced dose of each; non-human primate model; 10 different gene pathways | (Falzarano et al., 2013a, Falzarano et al., 2013b, Zheng and Wang, 2016) | ||
| IFN-β1b and lopinavir |
In vitro In vivo (Marmoset) |
Combination therapy- reduced dose of each | (Chan et al., 2015c) | |||
| IFN combination therapy (ribavirin and/or lopinavir | Case studies (human) | Only prophylactic or early use; insufficient evidence of clinical efficacy as yet | (Khalid et al., 2015, Kim et al., 2016b, Spanakis et al., 2014, Strayer et al., 2014) | |||
| IFN combination therapy (ribavirin) | Retrospective cohort studies (human) | Probable benefit of early use in less vulnerable patients; safety and efficacy established for other viral illnesses | Only prophylactic or early use; insufficient evidence of clinical efficacy as yet | (Al-Tawfiq et al., 2014, de Wilde et al., 2013, Khalid et al., 2014, Lau et al., 2013, Omrani et al., 2014, Shalhoub et al., 2015) | ||
| IFN combination therapy (cyclosporine) |
In vitro Human ex-vivo explant |
Synergistic effect; safety and efficacy established for other viral illnesses | (Li et al., 2018) | |||
| S protein host proteases | TMPRSS2 inhibitor | Camostat | In vivo- mouse, SARS-CoV | Already in clinical use | (Zhou et al., 2015b) | |
| TMPRSS2 inhibitor | Nafamostat | Split-protein-based cell–cell fusion assay | Already in clinical use | (Yamamoto et al., 2016) | ||
| Cathepsin L inhibitor | Teicoplanin dalbavancin oritavancin telavancin | High-throughput screening | Already in clinical use | (Zhou et al., 2016) | ||
| Viral proteases | PL(pro) inhibitor | 6-mercaptopurine (6MP) 6-thioguanine (6TG) |
In vitro | Potential for more MERS-specific agents | (Cheng et al., 2015) | |
| PL(pro) inhibitor | F2124–0890 | In vitro | May lose potency in physiological reducing environments | (Clasman et al., 2017) | ||
| Mpro | Lopinavir |
In vitro In vivo (marmosets) |
High activity at low micromolar range in vitro; better outcomes, in marmosets | Clinical efficacy not fully established in humans | (Chan et al., 2015, de Wilde et al., 2014, Rambaut, 2014) |