Where the program starts
You need a screen
We run a replicon assay in the right cell line, with viability in the same well. You get dose-response data that separates activity from toxicity.
You have hits, not a target
Resistance selection and reverse genetics name the target. You get a resistance profile before chemistry commits.
You need the whole program
Screening, chemistry, structure, DMPK and in vivo, as one team on one site. We have run our own antiviral program to oral efficacy.
A replication model you can screen safely
A replicon is a viral genome with its structural genes removed and a reporter put in their place. It replicates. It cannot infect. It reports inhibitors of viral replication and of the individual enzymes that drive it.
Step 01 of 05
Design
Structural genes come out. A reporter goes in.
Step 02 of 05
Assemble
Genome modification, assembly and cloning produce the construct.
Step 03 of 05
Transcribe
In vitro transcription generates the replicon RNA, with QC on the transcript.
Step 04 of 05
Deliver
Transfection, electroporation or nucleofection into the target line. A transient model reads out here.
Step 05 of 05
Establish
For a stable model, antibiotic selection and single-cell cloning isolate and characterize the clone.
Nine models. Seven viruses.
And the one you need next.
The panel below is what runs today. Replicons are designed and built in-house, so a virus, serotype or cell background that is not on the list can be added to it.
Stable clones give a screening-grade signal and the background for selecting resistance. Transient models stand up faster.
From phenotypic activity to an identified and validated target
Step 01
Compound pressure selects resistant clones.
Output: A resistant replicon line, maintained under compound pressure.
Step 02
Sequencing identifies the mutation.
Output: The variant called against the parental sequence. In the Zika program that was I156T in NS3.
Step 03
Reverse genetics puts it back into a wild-type replicon to confirm it.
Output: A wild-type replicon carrying the mutation, reproducing the resistance.
Step 04
The target is produced recombinantly and tested in a biochemical assay.
Output: Recombinant target protein and a dose-response on the isolated enzyme.
Step 01
CRISPR/Cas9 removes the candidate host factor.
Output: A knockout line, with the edit verified by sequencing.
Step 02
Replication efficiency is measured in the knockout.
Output: Replication in the knockout, measured against the parental line.
Step 03
A change answers the same question from the host side.
Output: The host factor’s contribution to replication, quantified.
IRBM-Z-2: A First-in-Class Antiviral Against Zika
Infectious Disease · Internal Program
Zika remains a persistent global health threat, linked to microcephaly in newborns and Guillain-Barré syndrome in adults, with no approved antiviral or vaccine available.
IRBM-Z-2 bound in the allosteric pocket of the ZIKV NS2B-NS3 protease
The breakthrough
From a 121K-compound phenotypic screen to a structure-guided, orally bioavailable NS2B-NS3 protease inhibitor with a novel allosteric mechanism, with activity across related flaviviruses (Dengue, West Nile).
The integrated approach
Screening, chemistry, structure, DMPK and in vivo, as one team on one site.
Published in Nature Communications (2026) and the Journal of Medicinal Chemistry (2026), opening new opportunities for flavivirus-targeted therapies.
Our heritage in helping develop medicines that have a global impact includes the marketed drug ISENTRESS®, for HIV, and Grazoprevir, a component of HCV ZEPATIER® combination therapy.
Move faster from target to preclinical candidate
IRBM’s Integrated Drug Discovery platform unites chemistry, biology, DMPK, and in vivo pharmacology under one scientific framework so candidates advance through fewer handoffs, stronger data continuity, and better-informed decisions.
Frequently Asked Questions
What is a viral replicon assay, and why use one instead of live virus?
A replicon is a viral genome with the structural genes removed. It replicates but cannot assemble infectious particles. A reporter gene inserted in their place makes replication quantifiable by luminescence. This allows compound testing at screening scale and in dose-response, without handling infectious virus.
Which viruses can IRBM screen against today?
Nine replication models across seven viruses: Zika, dengue serotype 2 (DENV-2), West Nile, chikungunya, HCV, SARS-CoV and SARS-CoV-2. These run in Vero, Huh7 and BHK-21 backgrounds, as stable clones or transient models. New replicons can be built for a virus not on the list.
Can IRBM identify the target of a hit from a phenotypic screen?
Yes. Compound pressure selects resistant clones and sequencing identifies the mutation. Reverse genetics puts that mutation back into a wild-type replicon to confirm it accounts for resistance. The target is then produced recombinantly and tested in a biochemical assay. Host factors are addressed by CRISPR/Cas9 knockout.
Can a program start with a single assay?
Yes. One replicon assay or one screening campaign is a complete engagement. Scope expands by milestone, integrated or standalone, with the same team throughout.
How is the work handled, and where?
All work runs at a single research site in Pomezia, Italy. Replicon constructs are non-infectious by design, which is what allows replication assays to run at screening scale and in miniaturized format. Viral genome engineering, in vitro transcription, nucleic acid workflows, compound testing, single-cell cloning and protein analytics are performed in house.
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