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The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), sparked an international debate on effective ways to prevent and treat the virus. Specifically, there were many varying opinions on the use of ivermectin (IVM) throughout the world, with minimal research to support either side. IVM is an FDA-approved antiparasitic drug that was discovered in the 1970s and was found to show antiviral activity. The objective of this study is to examine the binding behavior and rates of association and dissociation between SARS-CoV-2 receptor binding domain (RBD), IVM, and their combination using aminopropylsilane (APS) biosensors as surrogates for the hydrophobic interaction between the viral protein and human angiotensin-converting enzyme 2 (ACE2) receptors to determine the potential of IVM as a repurposed drug for SARS-CoV-2 prevention and treatment. The IVM, RBD, and combination binding kinetics were analyzed using biolayer interferometry (BLI) and validated with multiple in silico techniques including protein–ligand docking, molecular dynamics simulation, molecular mechanics-generalized Born surface area (MM-GBSA), and principal component analysis (PCA). Our results suggest that with increasing IVM concentrations the association rate with the hydrophobic biosensor increases with a simultaneous decrease in dissociation. Significant kinetic changes to RBD, when combined with IVM, were found only at a concentration a thousand times the approved dosage with minimal changes found over a 35-min time period. Our study suggests that IVM is not an effective preventative or treatment method at the currently approved dosage. [ABSTRACT FROM AUTHOR]

A novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified as the cause of the COVID-19 pandemic that originated in China in December 2019. Although extensive research has been performed on SARS-CoV-2, the binding behavior of spike (S) protein and receptor binding domain (RBD) of SARS-CoV-2 at different environmental conditions have yet to be studied. The objective of this study is to investigate the effect of temperature, fatty acids, ions, and protein concentration on the binding behavior and rates of association and dissociation between the S protein and RBD of SARS-CoV-2 and the hydrophobic aminopropylsilane (APS) biosensors using biolayer interferometry (BLI) validated with molecular dynamics simulation. Our results suggest three conditions—high ionic concentration, presence of hydrophobic fatty acids, and low temperature—favor the attachment of S protein and RBD to hydrophobic surfaces. Increasing the temperature within an hour from 0 to 25 °C results in S protein detachment, suggesting that freezing can cause structural changes in the S protein, affecting its binding kinetics at higher temperature. At all the conditions, RBD exhibits lower dissociation capabilities than the full-length S trimer protein, indicating that the separated RBD formed stronger attachment to hydrophobic surfaces compared to when it was included in the S protein. [ABSTRACT FROM AUTHOR]

Low-temperature methane oxidation is one of the greatest challenges in energy research. Although methane monooxygenase (MMO) does this catalysis naturally, how to use this biocatalyst in a fuel cell environment where the electrons generated during the oxidation process is harvested and used for energy generation has not yet been investigated. A key requirement to use this enzyme in a fuel cell is wiring of the active site of the enzyme directly to the supporting electrode. In soluble MMO (sMMO), two cofactors, i.e., nicotinamide adenine di-nucleotide (NAD+) and flavin adenine dinucleotide (FAD) provide opportunities for direct attachment of the enzyme system to a supporting electrode. However, once modified to be compatible with a supporting metal electrode via FeS functionalization, how the two cofactors respond to complex binding phenomena is not yet understood. Using docking and molecular dynamic simulations, modified cofactors interactions with sMMO-reductase (sMMOR) were studied. Studies revealed that FAD modification with FeS did not interfere with binding phenomena. In fact, FeS introduction significantly improved the binding affinity of FAD and NAD+ on sMMOR. The simulations revealed a clear thermodynamically more favorable electron transport path for the enzyme system. This system can be used as a fuel cell and we can use FeS-modified-FAD as the anchoring molecule as opposed to using NAD+. The overall analysis suggests the strong possibility of building a fuel cell that could catalyze methane oxidation using sMMO as the anode biocatalyst. [ABSTRACT FROM AUTHOR]