EPITHELIX

In Vitro Evaluation of antivirals using airway tissues


1. MucilAir™ and SmallAir™, platforms to evaluate many viral infection related end points

Respiratory viral infections cause mild to severe diseases worldwide, such as common cold, bronchiolitis and pneumonia and are associated with huge costs for society. To test new molecules for shortening, alleviating the diseases or to develop new therapies, relevant human models are mandatory. MucilAir™ and SmallAir™, holds in vitro specific mechanisms to counter invaders comparable to the in vivo situation, such as mucus production, mucociliary clearance, and secretion of defensive molecules.

Virus
x Virus

Contract us to evaluate the efficiency of your novel antivral coumpound on the following clinical viral strains

Rhinovirus
Rhinovirus
HRV-A 16/49/55
HRV-B 14/48
HRV-C15/8/11
Influenza
Influenza
Influenza A (H1N1 and H3N2)
Respiratory Enterovirus
Respiratory Enterovirus
EV-68
Coronavirus
Coronavirus
Coronavirus (OC 43)
Respiratory Syncytial Virus
Respiratory Syncytial Virus
Respiratory Syncytial Virus
Others
Others
Métapneumovirus

2. Testing strategy



3. Efficient Replication of difficult to grown viruses

A panel of clinical rhinovirus (RV), respiratory enterovirus (EV), influenza virus (Flu), respiratory syncytial virus (RSV) and coronavirus (HCoV) specimens are all capable of productive infection in MucilAir™. The virions enter and exit preferentially through the apical surface (Tapparel et al., Virology, 2013 Nov; 446:1-8). Thus, MucilAir™ is a relevant, reliable, and convenient tool for replicating respiratory viruses, including the most challenging ones

Replication
x Replication

Efficient replication of various clinical virus strains using MucilAir™ exponential phase, pic of infection

4. Localization of the replications

HRV-C15
HRV-C15
HRV-C15 is colocalized with ciliated cells
EV-68
HRV-C15
EV-68 is colocalized with ciliated cells
HRV-A49
HRV-A49
HRV-A49 is colocalized with ciliated cells
H3N2
HRV-C15
H3N2 is colocalized with goblet cells
Localization of the virus replication:
In Red: virus colocalization, In blue, Nucleus, in green Ciliated cells except for H3N2: goblet cells

5. Inhibition of virus replication

viral inhibition on infected Mucilair
x viral inhibition on infected Mucilair

Inhibition of HRV-A16 by Rupintrivir and H1N1 by Oseltamivir
Rupintrivir dose-reponse in cell extract at Day 1 for HRV C15
x Rupintrivir dose-reponse in cell extract at Day 1 for HRV C15
Rupintrivir dose-reponse in cell extract at Day 1 for HRV A16
x Rupintrivir dose-reponse in cell extract at Day 1 for HRV A16

The replication of the HRV A16, B14, C15 and EV-D68 is inhibited by Rupintrivir in a dose dependent manner in the MucilAir™ cultures.

Thus, MucilAir™ is a relevant, reliable, and convenient tool for testing and ranking novel anti-viral drugs against the respiratory viruses, including the most challenging ones

6. Restore of the impaired barrier function (TEER)

HRV C15, H3N2 and H1N1 induced transient decrease in TEER inhibition which can be prevented by Rupintrivir or Oseltamivir treatment.

7. Restore of the impaired Mucociliary function

Mucociliary clearance upon rhinovirus infection
x Mucociliary clearance upon rhinovirus infection

Concomitant apical inoculation of HRV A16, B14 and C15, with 5 mM of Rupintrivir in the basolateral medium. Mucociliary clearance measurements were performed at Day 2 and 4 at 33°C
Mucociliary clearance upon EV-D68 infection at Day 4
x Mucociliary clearance upon EV-D68 infection at Day 4

EV-D68 induced impairment of mucociliary clearance is prevented by Rupintrivir.

References


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