The miRNA COMPLEXES AGAINST CORONAVIRUSES SARS-CoV-2, SARS-CoV, and MERS-CoV

Background: In the past twenty years humankind has effected from infections caused by SARS-CoV (severe acute respiratory syndrome), MERS-CoV (Middle East respiratory syndrome) and SARS-CoV-2 coronaviruses, which have caused significant harm to human health and resulted in high mortality. The possibility of using miRNA (mRNA-inhibiting RNA) to inhibit infections caused by the coronaviruses SARS-CoV-2, SARS-CoV, and MERS-CoV has been shown. Methods: The MirTarget program determines the following characteristics of interaction between miRNAs and messenger RNAs (mRNAs): the start of the miRNA binding site on the mRNA; the locations of the miRNA binding sites in the 3'-untranslated region (3'UTR), 5'-untranslated region (5'UTR), or coding sequence (CDS); the interaction free energy (∆G, kJ/mole); and nucleotide interaction schemes between miRNAs and mRNAs.Results: Using bioinformatics approaches, completely complementary miRNA (cc-miRNA) complexes were predicted to be able to bind and inhibit the translation of coronavirus proteins and the replication of SARS-CoV-2, SARS-CoV, and MERS-CoV genomes. For complexes of seven completely complementary miRNA of SARS-CoV-2 (cc-miRc), seven completely complementary miRNA of SARS-CoV (cc-miRs), and eight completely complementary miRNA of MERS-CoV (cc-miRm), the interactions with the RNA genomes (gRNAs) of the corresponding coronaviruses was evaluated. The free energy of the interactions of cc-miRNAs with binding sites was significantly higher than the free energy of the interactions with other regions in gRNA, which ensures high selectivity of the binding of cc-miRNAs. Weak binding of cc-miRNAs to the mRNAs of 17508 human genes was shown, which suggests the absence of side effects of the cc-miRNAs in humans. A feature of this method is the simultaneous inhibition of translation and replication by several cc-miRNAs binding from the 5' end to the 3' end of gRNA. Conclusion: The use of several cc-miRNAs to suppress infections allows each of them to be used at a lower concentration to avoid side effects when one cc-miRNA is introduced into humans at a high concentration.

The miRNA Complexes Against Coronaviruses COVID-19, SARS-CoV, And MERS-CoV

Background: In the past twenty years humankind has effected from infection caused by SARS-CoV (severe acute respiratory syndrome), MERS-CoV (Middle East respiratory syndrome) and COVID-19 coronaviruses, which have caused significant harm to human health and resulted in high mortality. The possibility of using miRNA (mRNA-inhibiting RNA) to inhibit infections caused by the coronaviruses COVID-19, SARS-CoV, and MERS-CoV has been shown. Methods: The MirTarget program determines the following characteristics of interaction between miRNAs and messenger RNAs (mRNAs): the start of the miRNA binding site on the mRNA; the locations of the miRNA binding sites in the 3'-untranslated region (3'UTR), 5'-untranslated region (5'UTR), or coding sequence (CDS); the interaction free energy (∆G, kJ/mole); and nucleotide interaction schemes between miRNAs and mRNAs. Results: Using bioinformatics approaches, completely complementary miRNA (cc-miRNA) complexes were predicted to be able to bind and inhibit the translation of coronavirus proteins and the replication of COVID-19, SARS-CoV, and MERS-CoV genomes. For complexes of seven completely complementary miRNA of COVID-19 (cc-miRc), seven completely complementary miRNA of SARS-CoV (cc-miRs), and eight completely complementary miRNA of MERS-CoV (cc-miRm), the interactions with the RNA genomes (gRNAs) of the corresponding coronaviruses was evaluated. The free energy of the interactions of cc-miRNAs with binding sites was significantly higher than the free energy of the interactions with other regions in gRNA, which ensures high selectivity of the binding of cc-miRNAs. Weak binding of cc-miRNAs to the mRNAs of 17508 human genes was shown, which suggests the absence of side effects of the cc-miRNAs in humans. A feature of this method is the simultaneous inhibition of translation and replication by several cc-miRNAs binding from the 5' end to the 3' end of gRNA. Conclusion: The use of several cc-miRNAs to suppress infections allows each of them to be used at a lower concentration to avoid side effects when one cc-miRNA is introduced into humans at a high concentration.

A protein interaction free energy model based on amino acid residue contributions: Assessment of point mutation stability of T4 lysozyme

Here we present a model to estimate the interaction free energy contribution of each amino acid residue of a given protein. Protein interaction energy is described in terms of per-residue interaction factors, [Formula: see text]. Multibody interactions are implicitly captured in [Formula: see text] through the combination of amino acid terms ([Formula: see text]) guided by local conformation indices ([Formula: see text]). The model enables construction of an interaction factor heat map for a protein in a given fold, allows prima facie assessment of the degree of residue–residue interaction, and facilitates a qualitative and quantitative evaluation of protein association properties. The model was used to compute thermal stability of T4 bacteriophage lysozyme mutants across seven sites. Qualitative assessment of mutational effects provides a straightforward rationale regarding whether a particular site primarily perturbs native or non-native states, or both. The presented model was found to be in good agreement with experimental mutational data ([Formula: see text]) and suggests an approach by which to convert structure space into energy space.

Interactions between biological membranes: theoretical concepts

In this chapter we review the various types of generic (non-specific) forces acting between lipid membranes in an aqueous environment and discuss the underlying mechanisms, with particular focus on the competing roles of enthalpic and entropic contributions. The interaction free energy (or interaction potential) is typically the result of a subtle interplay of several, often antagonistic contributions with comparable magnitude. First, we will briefly introduce the underlying physics of various kinds of surface–surface interactions, starting with theories of van der Waals and undulation interactions, covering electrostatics, depletion, and order–parameter fluctuation effects as well. We then turn our attention to a strong and universal repulsive force at small membrane–membrane separations, namely the hydration interaction. It has been under debate and investigation for decades and is not well captured by continuum approximations, thus here we will mainly rely on atomistic simulation techniques.