The N501Y and K417N mutations in the spike protein of SARS-CoV-2 alter the interactions with both hACE2 and human derived antibody: A Free energy of perturbation study
Link to bioRxiv
The R346K Mutation in the Mu Variant of SARS-CoV-2 Alter the Interactions with Monoclonal Antibodies from Class 2: A Free Energy of Perturbation Study
Link to bioRxiv
Micar Innovation is a drug discovery factory. The company has found a niche where it is able to create a large societal impact by improving the quality of life through discovery novel blockbuster drug molecules for a large class of diseases (Pipeline). Micar Innovation focuses on entire drug discovery process using improved structure based insilico drug design from scratch till Preclinical phase with advanced predictions of activity, selectivity and ADMET:
We find the target protein which is involved in certain disease (usually membrane proteins)and then design highly quality 3D structure by intensive Molecular dynamics (cMD) and advanced sampling approaches such as aMD and Metadynamics; Our targets are usually orphan GPCRs, understudied proteins and other targets that relate to rare diseases and can be useful for development of drug candidates for both human and veterinary medicine.
(In a case when both the structure and dynamics of some protein are not clear we use state of art Molecular dynamics simulations such as long term classical (cMD), accelerated (aMD), GaMD and Metadynamics to obtain the information, which is critical for the drug discovery project to be performed. For instance, if you have GPCR structure created by Homology modeling you will need to refine it and to obtain a really good structure which further to be used during the virtual screens and FEP calculations.)
We have more than 70% success rate, i.e. from 10 predicted to be active ligands at least 7 are active after performing the experimental tests. Our innovation in this area is based on the combination of structural based pharmacofore and docking virtual screening. New hit compounds discovery by state of art approaches (more than 70% success rate) An example: To novel GlyT2 leads with <0.5μM activity. We perform virtual screening of 800 million molecules from ZINC15, Enamine, Chembridge, etc. databases by our newly developed approach that combines structure based pharmacophore and docking methodology.
Recently, we improved the Free Energy Perturbation (FEP+) Calculations by 50% increasing significantly the accuracy.Indeed many other approaches are also employed for this critical step, which is the most expensive part of any drug discovery project. Improved FEP+ guided lead optimization & computer guided ADMET property improvement 7-10 small highly potent and selective molecules with all predicted activity, selectivity and ADMET properties Novel drug candidate (small molecule) is ready to go into next Preclinical phase with great advanced predictions of activity, selectivity and ADMET – i.e. refined structure, absorptions, membrane penetration, low toxic potential, etc. to validate POC.
Preclinical phase with advanced predictions of activity, selectivity and ADMET (refined structure, absorptions, membrane penetration, low toxic potential, etc. to validate non-clinical Proof-of-Concepts).
Micar Innovation novel molecules has non-clinical Proof-of-Concepts achievements in therapeutic areas such as neuroscience, oncology, cardio-vascularity, dermatology, immunology (Pipeline). The business model is based on licensing our intellectual property to commercial partners or on the creation new spin out companies. The demonstration of true clinical proof-of-concept is a key value-creation step in the clinical development of a medicine.
Micar Innovation received the CIDIC award for its well-chosen positioning in a complex and long value chain, where it can create key-value contributions by delivering non-clinical POCs. The company can be qualified as a fountain of intellectual property and an IP broker for new pharma startups and big pharma industry.
In computer-aided drug design (CADD), the ultimate goal is to be able to predict accurately how strongly a potential drug compound will bind to a protein target (i.e., the compound’s binding affinity). Micar21 Drug Discovery platform able to do this, drug discovery to be significantly accelerated, since we would only need to synthesize in the lab those compounds with predicted high affinity for the target of interest (and predicted low affinity for proteins we didn’t want to interfere with).
We have our own drug discovery programs and our lead compounds are already in Drug Discovery & Preclinical studies. Our strategy is to develop drug for both: humans and companion animals.
*It takes about 7-12 months to obtain a license for companion animals drug.