Destructive effect of RNаse a on the SARS-CoV-2 virus (in vitro research)

BACKGROUND: For today, the most important and discussed issue in the professional medical community is the problem of prevention and treatment of a new coronaviral infection (COVID-19). The main reason for the non-decreasing increase in morbidity and mortality is the absence of an etiotropic drug. In our study, it is proposed to use a previously available drug for the treatment of tick-borne encephalitis, ribonuclease A, obtained from the pancreas of cattle. AIM: The aim of investigation was to study the antiviral activity of RNаse A against SARS-CoV-2 in in vitro experiments. MATERIALS AND METHODS: The experiment used samples of 50 patients with a confirmed (by PCR) primary diagnosis of a new coronoviral infection COVID-19. The preparation for the study was served by ribonuclease A (neoFroxx GmbH, Germany) at a concentration of 0.5; 1; 5 and 10 mg/ml, incubated at 4 and 37C, the exposure was 20 minutes, 20 hours. A set of reagents OTT-PCR-RV-SARS-CoV-2 (Syntol, Russia) was used as test systems. RESULTS: of the current study is the revealed antiviral activity of ribonuclease A at a minmal concentration of 0.5 mg/ml during incubation from 20 minutes to 20 hours, in the temperature range of 437C. CONCLUSIONS: The data obtained in the in vitro study confirmed the ability of ribonuclease A to destroy viral RNA, which suggests the possible use of the drug both for the treatment of patients and for the treatment of environmental objects.

Differential expression of RNASE4 in cancer of the vulva.

In these brief notes we document work using published microarray data (1, 2) to pioneer integrative transcriptome analysis comparing vulvar carcinoma to its tissue of origin, the vulva. We report the differential expression of ribonuclease A family member 4, encoded by RNASE4, in cancer of the vulva. RNASE4 may be of pertinence to understanding transformation and disease progression in vulvar cancer (3).

Ultrastructural immunocytochemistry shows impairment of RNA pathways in skeletal muscle nuclei of old mice: A link to sarcopenia?

During aging, skeletal muscle is affected by sarcopenia, a progressive decline in muscle mass, strength and endurance that leads to loss of function and disability. Cell nucleus dysfunction is a possible factor contributing to sarcopenia because aging-associated alterations in mRNA and rRNA transcription/maturation machinery have been shown in several cell types including muscle cells. In this study, the distribution and density of key molecular factors involved in RNA pathways namely, nuclear actin (a motor protein and regulator of RNA transcription), 5-methyl cytosine (an epigenetic regulator of gene transcription), and ribonuclease A (an RNA degrading enzyme) were compared in different nuclear compartments of late adult and old mice myonuclei by means of ultrastructural immunocytochemistry. In all nuclear compartments, an age-related decrease of nuclear actin suggested altered chromatin structuring and impaired nucleus-to-cytoplasm transport of both mRNA and ribosomal subunits, while a decrease of 5-methyl cytosine and ribonuclease A in the nucleoli of old mice indicated an age-dependent loss of rRNA genes. These findings provide novel experimental evidence that, in the aging skeletal muscle, nuclear RNA pathways undergo impairment, likely hindering protein synthesis and contributing to the onset and progression of sarcopenia.

Bis-Lactam Peptide [i, i+4]-Stapling with α-Methylated Thialysines

Four bis-lactam [i, i+4]-stapled peptides with d- or l-α-methyl-thialysines were constructed on a model peptide sequence derived from p110α[E545K] and subjected to circular dichroism (CD) and proteolytic stability assessment, alongside the corresponding bis-lactam [i, i+4]-stapled peptide with l-thialysine. The % α-helicity values of these four stapled peptides were found to be largely comparable to each other yet greater than that of the stapled peptide with l-thialysine. An l-α-methyl-thialysine-stapled peptide built on a model peptide sequence derived from ribonuclease A (RNase A) was also found to exhibit a greater % α-helicity than its l-thialysine-stapled counterpart. Moreover, a greater proteolytic stability was demonstrated for the l-α-methyl-thialysine-stapled p110α[E545K] and RNase A peptides than that of their respective l-thialysine-stapled counterparts.

Architectural RNA in chromatin organization

RNA plays a well-established architectural role in the formation of membraneless interchromatin nuclear bodies. However, a less well-known role of RNA is in organizing chromatin, whereby specific RNAs have been found to recruit chromatin modifier proteins. Whether or not RNA can act as an architectural molecule for chromatin remains unclear, partly because dissecting the architectural role of RNA from its regulatory role remains challenging. Studies that have addressed RNA's architectural role in chromatin organization rely on in situ RNA depletion using Ribonuclease A (RNase A) and suggest that RNA plays a major direct architectural role in chromatin organization. In this review, we will discuss these findings, candidate chromatin architectural long non-coding RNAs and possible mechanisms by which RNA, along with RNA binding proteins might be mediating chromatin organization.