Cellular stress and SARS-CoV-2

Background: SARS-CoV-2, the etiological agent responsible for COVID-19, is an RNA virus belonging to the Coronaviridae family. During the virus replication, viral components interact with the cellular machinery, inducing alterations in cell physiology, which contributes to viral pathogenesis. Method(s): A bibliographical research about cellular stress and SARS-CoV-2 was performed at NCBI/Pubmed. Result(s): In response to the infection, signaling pathways are activated in the host cell, the goal of these pathways being to restore homeostasis. If homeostasis is not recovered, the signaling leads to cell death activation. Among the best-characterized signaling pathways, the cellular stress pathways such as oxidative stress, UPR, and autophagy stand out, which are evolutionarily conserved and are also interconnected with each other. There is strong theoretical and experimental evidence of various interactions of some components of these pathways with different viral proteins of coronavirus, and some studies with SARS-CoV-2 have already been performed. In this review, we highlight some of the cellular pathways-virus characterized to date. Conclusion(s): The cellular pathways and their relationship to viral infections remains unclear. The study of these relationships might constitute an important target for new research and the development of antiviral therapies. Copyright © 2021, Revista Salus. All rights reserved.

Biology and genetic diversity of SARS-CoV-2, the causative agent of COVID-19

The infection generated by SARS-CoV-2 has caused more than 200 million cases and 4.5 million deaths worldwide. SARS-CoV-2 has accumulated mutations that allow it to be classified into different lineages. Some of these lineages have been designated variants by the WHO: under monitoring (VUM), of interest (VOI), or of concern (VOC). Methodology. Different strategies for genomic surveillance of these SARS-CoV-2 variants have been described in each country. In Venezuela, the strategies include the amplification of a fragment of the spike, PCR-RFLP, and sequencing of the complete viral genome, which has allowed us to monitor the introduction of VOCs and VOIs to the country. Results. By October 2021, in Venezuela, the circulation of three VOCs, Alpha, Gamma, and Delta, and the two VOIs (Lambda and Mu) have been described. Globally, the Delta variant predominates in practically all continents except some Latin American countries, although it is estimated that it will soon prevail in the region as well. Discussion. The circulation of variants in the countries is a very dynamic process and Venezuela does not escape from this reality;therefore, it is important to continue genomic surveillance of this virus. Copyright © 2021, Revista Salus. All rights reserved.

Sub-lineages of the Omicron variant of SARS-CoV-2: characteristic mutations and their relation to epidemiological behavior

By the end of 2021, the Omicron variant of SARS-CoV-2, the coronavirus responsible for COVID-19, emerges, causing immediate concern, due to the explosive increase in cases in South Africa and a large number of mutations. This study describes the characteristic mutations of the Omicron variant in the Spike protein, and the behavior of the successive epidemic waves associated to the sub-lineages throughout the world. The mutations in the Spike protein described are related to the virus ability to evade the protec-tion elicited by current vaccines, as well as with possible reduced susceptibility to host proteases for priming of the fusion process, and how this might be related to changes in tropism, a replication enhanced in nasal epithelial cells, and reduced in pulmonary tissue;traits probably associated with the apparent reduced severity of Omicron compared to other variants. © 2022, Instituto de Investigaciones Clinicas. All rights reserved.

Detection of the Omicron variant of SARS-CoV-2 by restriction analysis targeting the mutations K417N and N440K of the spike protein

By the end of 2021, the Omicron variant of concern (VOC) emerges in South Africa. This variant caused immediate concern, due to the explosive increase in cases associated with it and the large number of mutations it exhibits. In this study, the restriction sites that allow detecting the mutations K417N and N440K in the Spike gene are described. This analysis al-lows us to propose a rapid method for the identification of cases infected with the Omicron variant. We show that the proposed methodology can contribute to provide more information on the prevalence and rapid detection of cases of this new VOC. © 2022, Instituto de Investigaciones Clinicas. All rights reserved.

A simple method for detection of mutations in amino acid 452 of the Spike protein of SARS-CoV-2 using restriction enzyme analysis

Variants of Concern or Interest of SARS-CoV-2 (VOC or VOI), the coronavirus responsible for COVID-19, have emerged in several countries. Mutations in the amino acid 452 of the Spike protein are particularly important and associated with some of these variants: L452R, present in Delta VOC, and L452Q, present in Lambda VOI. These mutations have been associated with both increased infectivity and evasion of protective immune response. A search on GISAID to detect the number of sequences harboring the L452R mutation and the frequency of Delta VOC among them, showed that since August 2021, most of these sequences belong to the Delta VOC. Restriction enzyme analysis is proposed as a rapid method to detect L452R. A small amplicon from the Spike gene was digested with MspI. A 100% concordance was observed between digestion and sequencing results. The mutation L452Q can also be detected by restriction analysis, allowing the identification of putative Lambda VOIs. The proposed methodology, which allows screening of a great number of samples, could provide a faster information on the prevalence of Delta VOC cases.