Table 3 Potency of RDV with concomitant medications commonly used in SUDV- and MARV-endemic regions tested in in vitro assays.

From: Expanded profiling of Remdesivir as a broad-spectrum antiviral and low potential for interaction with other medications in vitro

Category 1: Drugs with no innate activity against SUVD or MARV when tested in combination with RDV

Drug of interest (tested at fixed concentration1)

RDV activity against SUDV when in combination

RDV activity against MARV when combination

Drug-drug interaction? (RDV potency)

EC502 (µM)

CC50 (µM)

EC50 (µM)

CC50 (µM)

RDV alone

0.308 ± 0.313 (n = 9; 0.089, 0.936)

 > 2.5

0.109 ± 0.054 (n = 9; 0.037, 0.189)

 > 2.5

 

Acetaminophen (75 μM)

0.50 ± 0.56

 > 2.5

0.13 ± 0.02

 > 2.5

No

Amodiaquine (0.07 μM)

0.052 ± 0.044

 > 2.5

0.33 ± 0.10

 > 2.5

Enhanced5 for SUDV

Artemether (0.7 μM)

0.48 ± 0.55

 > 2.5

0.13 ± 0.03

 > 2.5

No

Artesunate (1.2 µM)

0.31 ± 0.45

 > 2.5

0.15 ± 0.03

 > 2.5

No

Artesunate (8.5 µM)

 < 0.02 (tox3)

 < 0.2

0.16 ± 0.06

 > 2.5

Atovaquone (3.7 µM)

0.094 ± 0.067

 > 2.5

0.08 ± 0.02

 > 2.5

No

Atovaquone (22.6 µM)

 < 0.02 (tox3)

 < 0.02

0.016 ± 0.006

 < 0.02

Ciprofloxacin (14 µM)

0.041 ± 0.002

 > 2.5

0.14 ± 0.03

 > 2.5

Enhanced for SUDV

Diazepam (1.7 µM)

0.50 ± 0.49

 > 2.5

0.11 ± 0.04

 > 2.5

No

Metronidazole (30 µM)

0.42 ± 0.46

 > 2.5

0.103 ± 0.005

 > 2.5

No

Omeprazole (3.2 µM4)

0.22 ± 0.19

 > 2.5

0.15 ± 0.07

 > 2.5

No

Ondansetron (0.3 µM)

0.40 ± 0.33

 > 2.5

0.12 ± 0.03

 > 2.5

No

Proguanil (3.2 µM)

0.57 ± 0.59

 > 2.5

0.16 ± 0.05

 > 2.5

No

Lamivudine (11.3 µM)

0.67 ± 0.75

 > 2.5

0.14 ± 0.06

 > 2.5

No

Lopinavir (15.6 µM)

See data below

See data below

0.29 ± 0.20

 > 2.5

No for MARV

Ritonavir (1.8 µM)

0.35 ± 0.34

 > 2.5

0.15 ± 0.05

 > 2.5

No

Tenofovir disoproxil fumarate (0.5 µM)

0.10 ± 0.04

 > 2.5

0.09 ± 0.03

 > 2.5

No

Category 2: Drugs with innate activity against SUDV or MARV when tested alone

 

Drug of interest

Activity against SUDV

Activity against MARV

EC50 (µM)

CC50 (µM)

EC50 (µM)

CC50 (µM)

Efavirenz

2.24 ± 0.57

20.7 ± 10.1

19.8 ± 0.1

15.1 ± 4.1

 

Lopinavir

2.32 ± 0.58

34.1 ± 0.9

 > 100

 > 100

 

Lumefantrine

9.60 ± 0.52

40.0 ± 1.2

16.6 ± 7.3

37.3 ± 0.9

 

Ceftriaxone

2.24 ± 0.57

20.9 ± 10.1

19.8 ± 0.1

15.1 ± 4.1

 

Drugs from Category 2 against SUDV or MARV when tested in combination with RDV

Drug of interest (tested at fixed concentration1)

RDV activity against SUDV when in combination

RDV activity against MARV when combination

Drug-drug interaction? (RDV potency)

EC502 (µM)

CC50 (µM)

EC50 (µM)

CC50 (µM)

Efavirenz (5 µM)

 < 0.015

 > 2.5

0.13 ± 0.13

 > 2.5

Not antagonistic

Efavirenz (11 µM)

ND

ND

0.075 ± 0.042

 > 2.5

Efavirenz (41 µM)

 < 0.02

 < 0.02

 < 0.02

 < 0.02

Lopinavir (15.6 µM)

 < 0.02

 > 2.5

0.29 ± 0.20

 > 2.5

Not antagonistic

Lumefantrine (12 µM)

0.026 ± 0.021

 > 2.5

0.103 ± 0.005

 > 2.5

Not antagonistic

Ceftriaxone (440 µM)

 < 0.017

 > 2.5

0.078 ± 0.011

 > 2.5

Not antagonistic

  1. Compounds are divided into two categories based on whether they have antiviral effects against SUDV or MARV as a single agent.
  2. ND not determined.
  3. 1Concentration equivalent to human plasma Cmax and has not been adjusted with protein-binding. Lower concentrations were used when significant cell killing was observed.
  4. 2EC50 values represent averages from 2–3 independent experiments.
  5. 3The observed antiviral effect is driven by cytotoxicity.
  6. 4Tested at concentration ~ 19-fold over reported Cmax (unadjusted for protein-binding).
  7. 5Enhanced activity is defined by > fivefold increase of antiviral activity of the combination over the RDV-alone treatment.
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