Nanosecond pulsed electric field (nsPEF) and vaccines: a novel technique for the inactivation of SARS-CoV-2 and other viruses?

Since the beginning of 2020, worldwide attention has been being focussed on SARS-CoV-2, the second strain of the severe acute respiratory syndrome virus. Although advances in vaccine technology have been made, particularly considering the advent of mRNA vaccines, up to date, no single antigen design can ensure optimal immune response. Therefore, new technologies must be tested as to their ability to further improve vaccines. Nanosecond Pulsed Electric Field (nsPEF) is one such method showing great promise in different biomedical and industrial fields, including the fight against COVID-19. Of note, available research shows that nsPEF directly damages the cell's DNA, so it is critical to determine if this technology could be able to fragment either viral DNA or RNA so as to be used as a novel technology to produce inactivated pathogenic agents that may, in turn, be used for the production of vaccines. Considering the available evidence, we propose that nsPEF may be used to produce inactivated SARS-CoV-2 viruses that may in turn be used to produce novel vaccines, as another tool to address 20 the current COVID-19 pandemic.Key MessagesViral inactivation by using pulsed electric fields in the nanosecond frequency.DNA fragmentation by a Nanosecond Pulsed Electric Field (nsPEF).Opportunity to apply new technologies in vaccine development.

Accessing gap-junction channel structure-function relationships through molecular modeling and simulations.

BACKGROUND: Gap junction channels (GJCs) are massive protein channels connecting the cytoplasm of adjacent cells. These channels allow intercellular transfer of molecules up to ~1 kDa, including water, ions and other metabolites. Unveiling structure-function relationships coded into the molecular architecture of these channels is necessary to gain insight on their vast biological function including electrical synapse, inflammation, development and tissular homeostasis. From early works, computational methods have been critical to analyze and interpret experimental observations. Upon the availability of crystallographic structures, molecular modeling and simulations have become a valuable tool to assess structure-function relationships in GJCs. Modeling different connexin isoforms, simulating the transport process, and exploring molecular variants, have provided new hypotheses and out-of-the-box approaches to the study of these important channels. METHODS: Here, we review foundational structural studies and recent developments on GJCs using molecular modeling and simulation techniques, highlighting the methods and the cross-talk with experimental evidence. RESULTS AND DISCUSSION: By comparing results obtained by molecular modeling and simulations techniques with structural and functional information obtained from both recent literature and structural databases, we provide a critical assesment of structure-function relationships that can be obtained from the junction between theoretical and experimental evidence.

New approaches for predicting protein retention time in hydrophobic interaction chromatography.

Hydrophobic interaction chromatography (HIC) is an important technique for the purification of proteins. In this paper, we review three different approaches for predicting protein retention time in HIC, based either on a protein's structure or on its amino-acidic composition, and we have extended one of these approaches. The first approach correlates the protein retention time in HIC with the protein average surface hydrophobicity. This methodology is based on the protein three-dimensional structure data and considers the hydrophobic contribution of the exposed amino acid residues as a weighted average. The second approach, which we have extended, is based on the high correlation level between the average surface hydrophobicity of a protein's hydrophobic interacting zone and its retention time in HIC. Finally, a third approach carries out a prediction of the average surface hydrophobicity of a protein, using only its amino-acidic composition, without knowing its three-dimensional structure. These models would make it possible to test different operating conditions for the purification of a target protein by computer simulations, and thus make it easier to select the optimal conditions, contributing to the rational design and optimization of the process.