We utilize as well as develop novel state-of-the-art nano-tools and nano-technologies to address above problems. If you want to discuss more along the research lines, please do contact us. This research requires developing skill set in a variety of fields, from physics, optics, chemistry and surface chemistry, cleanroom based nano fabrication, computer programming, modelling & interfacing, ultra-low-noise electronics, optical microscopy, theoretical modeling, molecular biology, microfluidics, DNA and protein engineering, cell biology, single molecule detection using nanopore platform, single molecule force measurements using Laser Optical Tweezers and Atomic Force Microscope as well as molecular visualization using different fluorescence methods.
The high technological complexity of products and services is a feature of the health sector. Therefore, the relationship between the scientific base of universities and institutes and the pharmaceutical industry is a necessary condition for national technological advances in this segment. One strategy already adopted and consolidated by the countries that are at the cutting edge of technological development and that, from the advent of the Innovation Law - Law 10.973/2004 - has been increasingly embraced by Brazilian institutions and Fiocruz is one of the most prominent health institutions from Brazil immersed in the research innovation challenges.
Fiocruz produces, disseminates, and share knowledge and technologies and contributes to the promotion of health and quality of life of the population. Besides the reduction of social inequalities and the national dynamics of innovation, with the defense of the right to health and full citizenship as central values, it uses science and innovation as the basis of socio-economic development and health promotion.
COVID 19, HIV-1, HIV-1 / 2, Chagas’ disease, dengue fever, leishmaniasis, leptospirosis, arboviruses, influenza, and many other diseases are under research at Instituto Oswaldo Cruz. Please take a look at the technological showcase in COVID 19, shared in the links to the research work window.
We want to provide example of science validation of the capability and speed of Micar21 Drug Discovery Platform, which can be viewed and validated through science publications. Early of December no one had accurate data on the effect of the new Covid19 - UK & South Africa mutations on the action of vaccines and on the binding of the virus to ACE2, so Micar21 decided to calculate pro-bono and support science worldwide. On 16.12.2020 - Micar21 starts insilico calculations. On 26.12.2020 - first version of our science publication - with calculation for English mutation COVID19. On 31.12.2020 - second version of our science publication - with calculation for South African mutation COVID19 is included and we published our scientific publication: https://www.biorxiv.org/content/10.1101/2020.12.23.424283v2.article-metrics Dr. Filip Fratev (Micar21) is the sole author of the science publication. In less than 5 months there are already 22 citations (very good result). Our competitors appeared with insilico data for Covid19 Mutations at the end of January 2021 (can be traced through science publications) On 14.02.2021 (sent on 14.02.2021 - published on 23.02.2021) science publication by Oxford, validates Micar21 insilico results with experimental data: https://www.cell.com/cell/pdf/S0092-8674(21)00226-9.pdf Here, through the experimental data, our Micar21 insilico data calculated in December 2020 are proved. Micar21 predicted in silico the stronger N501Y mutant binding to ACE2 (-1.42 kcal/mol) whereas months later experimental data shown a value of (-1.40 kcal/mol), thus, confirming that our in silico results was precise. The aim of Micar21 study and new paper was to provide urgently high quality data about the effect of the UK and South African mutations. However, during the process of revision of the paper many experimental studies became available which was an excellent opportunity for a validation of the in silico approaches employed here and in particular protein-protein FEP. Also, we can compare our results to other data obtained by theoretical approaches which can be viewed and validated through other science publications and showed in our new science publication in Journal of Chemical Information and Modelling - under final review: http://micar21.com/Covid19_UK_SA_mutation.pdf
22 NOV 2021 Micar21 publish at Journal of Chemical Information and Modeling
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 Retrospective Study
https://pubs.acs.org/doi/10.1021/acs.jcim.1c01242
27 Nov 2021 / 3:08 CET Filip Fratev / Micar Innovation (Micar21)
The new B.1.1.529 SARS-CoV-2 lineage (Omicron) looks really terrible with totally 7 mutations located at the RBD-ACE2 binding surface. To urgently provide a high quality data we are performing with Suman Sirimulla (UTEP) a Free energy of Perturbation (FEP) assessments of the impact of all mutations. The FEP method has been shown in our previous studies to be highly accurate for Alpha (1) and Mu (2) variants. We have already calculated that the G496S mutation lead to an additional increase in the RBD-ACE2 binding by 4 times in comparison to the presence of only N501Y mutation (Alpha variant). The latter mutation is included in our set up, thus we can conclude that G496S plus N501Y mutations result in a totally of 11 times increase of the RBD-ACE2 binding.
We plan to calculate the binding to ACE2 of all individual B.1.1.529 mutations and their total effect. Also, we will assay how these mutations will impact various antibody classes. We will keep you updated!
(1) 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 Retrospective Study - https://pubs.acs.org/doi/10.1021/acs.jcim.1c01242 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 - https://www.biorxiv.org/content/10.1101/2020.12.23.424283v2
(2) - 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 - https://www.biorxiv.org/content/10.1101/2021.10.12.463781v1
https://www.linkedin.com/feed/update/urn%3Ali%3Aactivity%3A6870177115547963392/
28 Nov 2021 / 6:24 CET Filip Fratev / Micar Innovation (Micar21)
Our preliminary FEP data showed that the SARS-CoV-2 Omicron’s (B.1.1.529 lineage) Q498R, Y505H and G496S mutations drastically increase the binding to ACE2, which is an indication of its transmission. They enhanced the binding by 98, 14 and 13 times, respectively, which transforms the S1-RBD to a picomolar binder! Our estimations are based on the structures of both Alpha and Beta variants. The K417N and T478K had a relatively small negative effect to the binding: ddG=0.44 and +0.16 kacl/mol, respectively. Initially, we are calculating the contribution of the individual mutations to the RBD-ACE2 interactions and next we will do that for their total cumulative effect. Also, we expect an improvements of the results after the multi-site FEP calculations due to the cycle closure data. Currently, we observed a difference only for G496S which has a ddG= -0.82 and -0.23 kcal/mol in Alpha and Beta variants, most likely due to the not good convergence in Beta. We will improve that during the next hours and expect the data for Q493K. The latter and Glu484Ala and Lys417Asn can be described as an individual hot spot of mutations.
https://www.linkedin.com/feed/update/urn:li:activity:6870177115547963392/
29 Nov 2021 / 6:49 CET Filip Fratev / Micar Innovation (Micar21)
We received almost the all FEP data for the Omicron’s RBD-ACE2 binding. It is clear now that the Q498R and Q493K are the main players in these interactions. However, there is a competition between them leading to decrease of the total binding; i.e. similar to case of N501Y and K417N tandem of mutations in Beta variant. What is exactly this decrease we will know soon but the ddG of Q493K has a positive value. The transformation of not charged to charged residues in known to produce a significant bias in FEP calculations. This is valid indeed for both Q498R and Q493K. Thus, we developing a special protocol in order to describe these significant changes which are responsible for the RBD-ACE2 binding in Omicron. In addition, our results shown that the N440K and G446S have indeed a small effect to the RBD-ACE2 interactions and the ddG values were -0.2 and +0.21 kcal/mol; i.e. in frame of possible error. We expected the G446S in a combination with G498R and surrounding residues additionally may stabilize this constellation of harmful mutations and in particular Arg498 but this turn out to be not true (ddG=0.24).
https://www.linkedin.com/feed/update/urn:li:activity:6870982318018854912/
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