The Role of Antigen Rapid Diagnostic Test in COVID-19 Diagnosis

Since the emergence of a novel infection due to the SARS-CoV-2 virus (COVID-19), the World Health Organization has urged countries to develop diagnostic tests to combat the pandemic. Molecular assays were developed following the release of the gene sequence of the virus in January 2020. Reverse transcription-quantitative PCR (RT-qPCR) is taken as the gold standard for the diagnosis of COVID-19. However, due to its limitations, highly sensitive methods for detecting antigens (antigen rapid diagnostic tests) have been developed that would help in a timely and accurate diagnosis. Antigen rapid diagnostic tests (Ag-RDTs) can help guide patient management at the point of care by random screening, re-testing, and timely decision-making in the field of public health. When the affordability and validity of the diagnostic assay are involved, no assay can show 100% correct results. Further studies need to be done to better understand the response of the Ag-RDTs in different settings. Nevertheless, Ag-RDTs can play a complementary role in the response and case management of COVID-19.

Beauvericin: The Journey of a Pesticide into a Humanized Drug

Drug discovery has been initially attributed to coincidence or trial and error where the traditional approach was complex, lengthy, and expensive. Conventional drug discovery methods require the costly random screening of synthesized compounds or natural products. Another downside for this approach is the wide dependency on the experimental use of animals for in vi-vo testing. Currently, in silico modeling has become a vital tool for drug discovery and repurposing, and molecular docking is being used to find the best matching between a ligand and a molecule. Practical application of in silico docking will predict the biomolecular interactions between the drug and the target host. Beauvericin (BEA) is an emerging mycotoxin produced by the entomopathogenic fungus Beauveria bassiana. Originally investigated for its pesticide capability, BEA is now considered as a molecule of interest for its potentially diverse biotechnological applications in the pharmacological industry and the field of medicine. In this manuscript, we will provide an overview of the repurposing of BEA into a potentially superior therapeutic molecule in a broad range of diseases. Furthermore, considerable attention has been given to the fundamental role of in silico techniques to i) further investigate the spectrum of this secondary metabolite and ii) elucidate the pathways of BEA for its promising therapeutic action

Regular universal screening for SARS-CoV-2 infection may not allow reopening of society after controlling a pandemic wave

BackgroundTo limit societal and economic costs of lockdown measures, public health strategies are needed that control the spread of SARS-CoV-2 and simultaneously allow lifting of disruptive measures. Regular universal random screening of large proportions of the population regardless of symptoms has been proposed as a possible control strategy.MethodsWe developed a mathematical model that includes test sensitivity depending on infectiousness for PCR-based and antigen-based tests, and different levels of onward transmission for testing and non-testing parts of the population. Only testing individuals participate in high-risk transmission events, allowing more transmission in case of unnoticed infection. We calculated the required testing interval and coverage to bring the effective reproduction number due to universal random testing (Rrt) below 1, for different scenarios of risk behavior of testing and non-testing individuals.FindingsWith R0 = 2.5, lifting all control measures for tested subjects with negative test results would require 100% of the population being tested every three days with a rapid test method with similar sensitivity as PCR-based tests. With remaining measures in place reflecting Re = 1.3, 80% of the population would need to be tested once a week to bring Rrt below 1. With lower proportions tested and with lower test sensitivity, testing frequency should increase further to bring Rrt below 1. With similar Re values for tested and non-tested subjects, and with tested subjects not allowed to engage in higher risk events, at least 80% of the populations needs to test every five days to bring Rrt below. The impact of the test-sensitivity on the reproduction number is far less than the frequency of testing.InterpretationRegular universal random screening followed by isolation of infectious individuals is not a viable strategy to reopen society after controlling a pandemic wave of SARS-CoV-2. More targeted screening approaches are needed to better use rapid testing such that it can effectively complement other control measures.FundingRECOVER (H2020-101003589) (MJMB), ZonMw project 10430022010001 (MK, HH), FCT project 131_596787873 (GR). ZonMw project 91216062 (MK)

Identification and Estimation of Undetected COVID-19 Cases Using Testing Data from Iceland

In the early stages of the COVID-19 pandemic, international testing efforts tended to target individuals whose symptoms and/or jobs placed them at a high presumed risk of infection. Testing regimes of this sort potentially result in a high proportion of cases going undetected. Quantifying this parameter, which we refer to as the undetected rate, is an important contribution to the analysis of the spread of the SARS-CoV-2 virus. We show that partial identification techniques can credibly deal with the data problems that common COVID-19 testing programs induce (i.e. excluding quarantined individuals from testing and low participation in random screening programs). We use public data from two Icelandic testing regimes during the first month of the outbreak and estimate an identified interval for the undetected rate. Our main approach estimates that the undetected rate was between 89% and 93% before the medical system broadened its eligibility criteria and between 80% and 90% after.

Molecular modelling and evaluation of antihyperthyroid drug compound

Drug targeting will play an essential function in drug discovery in the coming years, as the amount of structural records on protein targets keeps to rise. However, the conventional technique of drug discovery, primarily based upon random screening and systematic amendment of leads through medicinal chemistry strategies, will probably no longer to be deserted absolutely because it has doubtlessly vital advantages over shape-based strategies-specifically leads diagnosed in this way are unlikely to show a near resemblance to the herbal Ligand or substrate. They might also have gained in terms of patent novelty and selectivity. Such leads could then function the basis of structure-based totally, rational amendment programs, wherein their interactions with target receptors are described and improved molecules are designed. In the present study, an attempt is made to find suitable and better analogues of drugs used in the treatment of hyperthyroidism.

A systematic capsid evolution approach performed in vivo for the design of AAV vectors with tailored properties and tropism

Adeno-associated virus (AAV) capsid modification enables the generation of recombinant vectors with tailored properties and tropism. Most approaches to date depend on random screening, enrichment, and serendipity. The approach explored here, called BRAVE (barcoded rational AAV vector evolution), enables efficient selection of engineered capsid structures on a large scale using only a single screening round in vivo. The approach stands in contrast to previous methods that require multiple generations of enrichment. With the BRAVE approach, each virus particle displays a peptide, derived from a protein, of known function on the AAV capsid surface, and a unique molecular barcode in the packaged genome. The sequencing of RNA-expressed barcodes from a single-generation in vivo screen allows the mapping of putative binding sequences from hundreds of proteins simultaneously. Using the BRAVE approach and hidden Markov model-based clustering, we present 25 synthetic capsid variants with refined properties, such as retrograde axonal transport in specific subtypes of neurons, as shown for both rodent and human dopaminergic neurons.

Towards a fully automated algorithm driven platform for biosystems design

Large-scale data acquisition and analysis are often required in the successful implementation of the design, build, test, and learn (DBTL) cycle in biosystems design. However, it has long been hindered by experimental cost, variability, biases, and missed insights from traditional analysis methods. Here, we report the application of an integrated robotic system coupled with machine learning algorithms to fully automate the DBTL process for biosystems design. As proof of concept, we have demonstrated its capacity by optimizing the lycopene biosynthetic pathway. This fully-automated robotic platform, BioAutomata, evaluates less than 1% of possible variants while outperforming random screening by 77%. A paired predictive model and Bayesian algorithm select experiments which are performed by Illinois Biological Foundry for Advanced Biomanufacturing (iBioFAB). BioAutomata excels with black-box optimization problems, where experiments are expensive and noisy and the success of the experiment is not dependent on extensive prior knowledge of biological mechanisms.

700. Identification and Whole-Genome Sequencing (WGS) of Meropenem-Vaborbactam (MV) Resistant Klebsiella pneumoniae (MVRKP) Among Patients Without Prior Exposure to MV: Collateral Damage

Background MV is a newly approved β-lactam/β-lactamase inhibitor combination (BLIC) for the treatment of complicated urinary tract infections (cUTI). Vaborbactam is a cyclic boronic acid BLI that was mainly developed as a potent inhibitor of KPC carbapenemases and other Ambler class A&C enzymes. Vaborbactam is inactive against metallo-β-lactamases (MBL) and certain Class D enzymes (e.g. OXA-2 and OXA-48). We encountered a case of MV-resistant Klebsiella pneumoniae (MVRKP)and sought to explore the various mechanisms of MV resistance within KP. Methods A 65-year-old nursing home resident with multiple prior hospitalizations and recent exposure to antibiotics (Timeline) developed sepsis secondary to carbapenem-resistant Klebsiella pneumoniae (CRKP) cUTI. WGS of the patient’s isolate was performed. This was followed by random screening for MV resistance and WGS of other isolates from a historical database. Results Results of WGS are seen in the table below. Sequencing of our patient’s isolate revealed strain ST258 with a premature stop in aa89 of OmpK35 as well as insertions at Gly134 and Asp135 (i.e., the GD repeat) of OmpK36. Furthermore, the KPC plasmid’s copy number was approximately five times higher than the chromosome. No mutations encoding efflux system AcrAB-TolC were found. Conclusion Resistance to MV in KP was found in isolates that predate the drug’s availability. Notably, resistance occurred in the absence of MBLs and OXAs. The mechanism seems to involve outer membrane porin mutations in OmpK35 and/or OmpK36. WGS is a useful tool in identifying the mechanism of resistance especially for newer agents. Disclosures All authors: No reported disclosures.