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Molecular Targets in the Chemotherapy of Coronavirus Infection.

ABSTRACT: In the pathogenesis of the infectious process in the respiratory tract by SARS, MERS, and COVID-19 coronaviruses, two stages can be distinguished: early (etiotropic) and late (pathogenetic) ones. In the first stage, when the virus multiplication and accumulation are prevalent under insufficient host immune response, the use of chemotherapeutic agents blocking the reproduction of the virus is reasonable to suppress the development of the disease. This article considers six major chemotherapeutic classes aimed at certain viral targets: inhibitors of viral RNA polymerase, inhibitors of viral protease Mpro, inhibitors of proteolytic activation of viral protein S allowing virus entry into the target cell, inhibitors of virus uncoating in cellular endosomes, compounds of exogenous interferons, and compounds of natural and recombinant virus-neutralizing antibodies. In the second stage, when the multiplication of the virus decreases and threatening pathological processes of excessive inflammation, acute respiratory distress syndrome, pulmonary edema, hypoxia, and secondary bacterial pneumonia and sepsis events develop, a pathogenetic therapeutic approach including extracorporeal blood oxygenation, detoxification, and anti-inflammatory and anti-bacterial therapy seems to be the most effective way for the patient's recovery.

SUBMITTER: Zhirnov OP

PROVIDER: S-EPMC7232917 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Molecular Targets in the Chemotherapy of Coronavirus Infection.

Zhirnov O P OP

Biochemistry. Biokhimiia 20200501 5

In the pathogenesis of the infectious process in the respiratory tract by SARS, MERS, and COVID-19 coronaviruses, two stages can be distinguished: early (etiotropic) and late (pathogenetic) ones. In the first stage, when the virus multiplication and accumulation are prevalent under insufficient host immune response, the use of chemotherapeutic agents blocking the reproduction of the virus is reasonable to suppress the development of the disease. This article considers six major chemotherapeutic ...[more]

PMID: 32571182

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Project description:Bovine coronavirus (BCoV) infection that causes disease outbreaks among farm animals, resulting in significant economic losses particularly in the cattle industry, has the potential to become zoonotic. miRNAs, which are short non-coding segments of RNA that inhibits the expression of their target genes, have been identified as potential biomarkers and drug targets, though this potential in BCoV remains largely unknown. We hypothesize that certain miRNAs could simultaneously target multiple genes, are significantly conserved across many species, thereby demonstrating the potential to serve as diagnostic or therapeutic tools for bovine coronavirus infection. To this end, we utilized different existing and publicly available computational tools to conduct system analysis predicting important miRNAs that could affect BCoV pathogenesis. Eleven genes including CEBPD, IRF1, TLR9, SRC, and RHOA, significantly indicated in immune-related pathways, were identified to be associated with BCoV, and implicated in other coronaviruses. Of the 70 miRNAs predicted to target the identified genes, four concomitant miRNAs (bta-miR-11975, bta-miR-11976, bta-miR-22-3p, and bta-miR-2325c) were found. Examining the gene interaction network suggests IL-6, IRF1, and TP53 as key drivers. Phylogenetic analysis revealed that miR-22 was completely conserved across all 14 species it was searched against, suggesting a shared and important functional role. Functional annotation and associated pathways of target genes, such as positive regulation of cytokine production, IL-6 signaling pathway, and regulation of leukocyte differentiation, indicate the miRNAs are major participants in multiple aspects of both innate and adaptive immune response. Examination of variants evinced a potentially deleterious SNP in bta-miR-22-3p and an advantageous SNP in bta-miR-2325c. Conclusively, this study provides new insight into miRNAs regulating genes responding to BCoV infection, with bta-miR-22-3p particularly indicated as a potential drug target or diagnostic marker for bovine coronavirus.

Dataset Information

Molecular Targets in the Chemotherapy of Coronavirus Infection.

Publications

Molecular Targets in the Chemotherapy of Coronavirus Infection.

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