Table 4.
Antivirals combination therapy target two or more proteins of the influenza virus.
| Drug Combinations | Target | Virus | Efficacy Evaluating Model | Clinical Advantage/Primary Outcome Measures | Ref. | Status | Clinicaltrials.gov ID |
|---|---|---|---|---|---|---|---|
| Oseltamivir + JNJ-63623872 | Neuraminidase& Cap-dependent endonuclease | A | Clinical | Reduce the influenza load | - | II | NCT03040141 |
| Baloxavir + Favipiravir | Cap-dependent endonuclease & RdRp | A | In vitro | Improved antiviral activity | [85] | - | - |
| Baloxavir + Oseltamivir | Cap-dependent endonuclease & Neuraminidase | A | In vivo | Against Baloxavir, PA-resistant influenza | [87,88] | - | - |
| Baloxavir + Oseltamivir | A | Clinical | Recruiting | - | II, III | NCT05170009 | |
| Baloxavir + Oseltamivir | A | Clinical | Recruiting | - | II | NCT04712539 | |
| Favipiravir + Oseltamivir | RdRp & neuraminidase | A & B | Clinical | Faster clinical improvement | [89] | - | - |
| Peramivir +Favipiravir | A | In vivo | Against the oseltamivir-resistant influenza virus infection | [90,91] | - | - | |
| Peramivir + Rimantadine | M2 ion channel & neuraminidase | A | In vivo | Synergistic antiviral effects. | [92] | - | - |
| Oseltamivir + Rimantadine | A | In vivo | Improved morbidity and mortality | [93] | - | - | |
| Oseltamivir + Amantadine | A | In vivo | Provided protection | [94] | |||
| Oseltamivir + Amantadine | A | Clinical | Appears safe | [95] | I | NCT00416962 | |
| Oseltamivir + Amantadine | A | Clinical | Terminated | - | II | NCT00830323 | |
| Oseltamivir +Amantadine + Ribavirin | M2 ion channel, neuraminidase & RdRp | A | In vivo | Synergistic activity | [96,97,98] | ||
| Oseltamivir + Amantadine + Ribavirin | A | In vivo | Reduce mortality and weight loss | [99] | - | - | |
| Oseltamivir + Amantadine + Ribavirin | A | Clinical | Effective in virus clearance | - | II | NCT00979251 | |
| Oseltamivir + Amantadine + Ribavirin | A | Clinical | significant decrease in viral shedding | [100] | II | NCT01227967 | |
| Oseltamivir + Amantadine + Ribavirin | A | Clinical | Reduce the influenza load | [101] | I, II | NCT00867139 |