Kirk McGregor's research while affiliated with University of California, Davis and other places

The pulmonary surfactant protein A (SP-A) is a constitutively expressed immune-protective collagenous lectin (collectin) in the lung. It binds to the cell membrane of immune cells and opsonizes infectious agents such as bacteria, fungi, and viruses through glycoprotein binding. SARS-CoV-2 enters airway epithelial cells by ligating the Angiotensin Converting Enzyme 2 (ACE2) receptor on the cell surface using its Spike glycoprotein (S protein). We hypothesized that SP-A binds to the SARS-CoV-2 S protein and this binding interferes with ACE2 ligation. To study this hypothesis, we used a hybrid quantum and classical in silico modeling technique that utilized protein graph pruning. This graph pruning technique determines the best binding sites between amino acid chains by utilizing the Quantum Approximate Optimization Algorithm (QAOA)-based MaxCut (QAOA-MaxCut) program on a Near Intermediate Scale Quantum (NISQ) device. In this, the angles between every neighboring three atoms were Fourier-transformed into microwave frequencies and sent to a quantum chip that identified the chemically irrelevant atoms to eliminate based on their chemical topology. We confirmed that the remaining residues contained all the potential binding sites in the molecules by the Universal Protein Resource (UniProt) database. QAOA-MaxCut was compared with GROMACS with T-REMD using AMBER, OPLS, and CHARMM force fields to determine the differences in preparing a protein structure docking, as well as with Goemans-Williamson, the best classical algorithm for MaxCut. The relative binding affinity of potential interactions between the pruned protein chain residues of SP-A and SARS-CoV-2 S proteins was assessed by the ZDOCK program. Our data indicate that SP-A could ligate the S protein with a similar affinity to the ACE2-Spike binding. Interestingly, however, the results suggest that the most tightly-bound SP-A binding site is localized to the S2 chain, in the fusion region of the SARS-CoV-2 S protein, that is responsible for cell entry Based on these findings we speculate that SP-A may not directly compete with ACE2 for the binding site on the S protein, but interferes with viral entry to the cell by hindering necessary conformational changes or the fusion process.

e18560 Background: COVID-19 has contributed to healthcare inequity amongst minorities and lower socioeconomic populations, while complicating present anti-cancer treatment regimens. Due to their immunocompromised status, cancer patients are at an increased risk of severe SARS-CoV-2 infection. While sentiment analysis via SM has seen vast growth among healthcare professional, deeper connection and management has been lacking. Given the higher usage of SM impressions and the increase in healthcare disparities especially at the intersection of oncology and COVID-19, the aim of this study was to develop a platform that can: (1) show that the relationships highlighted within these tweets can be realized in biomolecular interactions—specifically within the interaction between solid tumors and COVID-19; (2) use SM data to connect patients with clinical trials. Methods: To determine this relationship, ontologies, which are groupings of terms and related identifiers, such as genes, were created for general search terms, utilizing the Human Phenotype Ontology. They were then combined with “COVID-19” and used as search terms in Twitter’s Standard Search tool. The keywords with the most matches were then queried through clinicaltrials.gov and European Bioinformatics Institute’s (EBI) Protein Search Tool to find relevant clinical trials and proteins. Finally, the proteins found by the EBI protein search were run through the SwissModel Tool to find relevant protein structures before being used in binding using Polar+’s Binding Platform from Iff Technologies, which provides K values related to 50% inhibition for each medication or immunotherapy. This produced a set of disease-specific keywords that are related to top tweets, clinical trials, protein structures, and binding concentration values in relevant biomolecular pathways for the keyword set “Tumor COVID-19”. Results: The example shown in Table is produced via our platform, with keywords with tweet numbers greater than 95% of all tweets with connected keywords used. Conclusions: By utilizing SM with highly relevant keywords, this platform can combat healthcare inequity by connecting patients and their tweets to clinical trials and enhance literacy about their medical conditions, while providing a greater understanding of the biomolecular pathways involved.[Table: see text]

The use of hydroxychloroquine to aid in the disruption of the SARS-CoV-2 virus and to cure or at least treat the COVID-19 disease is recently being reviewed in various clinical trials worldwide, but with insufficient examination of the binding of human ACE2 to the viral spike. In order to understand and assess the efficacy of the drug or drug combination, this paper looks at the effect of the pharmaceutical drug hydroxychloroquine, as well as a common co-drug, azithromycin, on the SARS-CoV-2 spike-ACE2 complex by using virtualized quantum mechanical modeling to better characterize binding sites on the complex, assess the binding between these sites and the drug compounds, and enhance community PDB files. <br