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Koronavírus 2 vyvolávajúci ťažký akútny respiračný syndróm (SARS-CoV-2) a pandémia ochorenia COVID-19 (COrona VIrus Disease-19), ktoré je týmto vírusom zapríčinené, v priebehu polroka zmenili svet. Deficit efektívnej terapie COVID-19, spolu s jeho etiológiou, rezultovali v čase písania tejto publikácie do viac ako 500 000 potvrdených úmrtí a globálna ekonomika je na nevídanej, bezprecedentne nízkej úrovni s neznámymi krátkodobými a dlhodobými dôsledkami. Ingavirín je považovaný za netoxické širokospektrálne antivirotikum s komplexným mechanizmom pôsobenia. Zlúčenina bola pôvodne projektovaná pre profylaxiu a liečbu chrípky, ktorá je zapríčinená vírusmi chrípky antigénnych typov A a B a pre liečbu ďalších akútnych respiračných ochorení vyvolaných inými vírusmi. V publikácii je formulovaná hypotéza o účinnosti tejto molekuly obsahujúcej 1H-imidazol-4-ylový heterocyklus proti SARS-CoV-2. Aktivita by mohla súvisieť so schopnosťou derivátu interferovať so špecifickými heterogénnymi nukleárnymi ribonukleoproteínmi (napríklad s typom A1). Tieto špecifické RNA-viažuce proteíny vykazovali afinitu k nukleokapsidovému proteínu (N-proteínu) koronavírusu vyvolávajúceho ťažký akútny respiračný syndróm (SARS-CoV), ktorý sa vyznačuje vysokou homológiou s N-proteínom SARS-CoV-2 vyjadrenou sekvenčnou zhodou 90,25 %. Narušenie optimálnych interakcií medzi nukleárnymi ribonukleoproteínmi a nukleokapsidovým proteínom SARS-CoV-2 by mohli rezultovať do inhibície replikačného cyklu tohto vírusu. Aditívne imunomodulačné vlastnosti ingavirínu by mohli byť výhodné pre indukciu adaptívnej imunity hostiteľských buniek.
The Severe Acute Respiratory Coronavirus 2 (SARS--CoV-2) and Coronavirus Disease-19 (COVID-19) pandemic, caused by the virus, have changed the world in just half a year. Lack of effective treatment, coupled with etiology of COVID-19, has resulted in more than 500,000 confirmed deaths at the time of writing, and the global economy is at an unseen unprecedented low level with unknown near- and long-term consequences. Ingavirin has been considered a non-toxic broad-spectrum antiviral with a complex mechanism of action. The molecule was originally designed for the prophylaxis and treatment of flu caused by both Influenza A and B viruses and for the treatment of viral causes of acute respiratory illness. The article hypothesized that the efficiency of given 1H-imidazol-4-yl heterocyclic scaffold-containing compound against SARS-CoV-2 might be connected with its ability to interfere with specific heterogeneous nuclear ribonucleoproteins (A1, for example). These specific cellular RNA-binding proteins showed affinity to Severe Acute Respiratory Coronavirus (SARS-CoV) nucleocapsid (N) protein, which shared high homology with the N protein of SARS-CoV-2 and the fact was expressed by a sequence identity of 90.52%. Impairing of the interactions between nuclear ribonucleoproteins and nucleocapsid (N) protein of SARS-CoV-2 might result in the inhibition of a viral replication cycle. Additional immunomodulating properties of ingavirin could be favorable for induction of adaptive immunity of host cells.
- Klíčová slova
- SARS-CoV2, ingavirin,
- MeSH
- antivirové látky farmakologie terapeutické užití MeSH
- Betacoronavirus účinky léků MeSH
- COVID-19 * MeSH
- farmakoterapie COVID-19 MeSH
- heterogenní jaderné ribonukleoproteiny MeSH
- imidazoly terapeutické užití MeSH
- kapronáty terapeutické užití MeSH
- koronavirové infekce farmakoterapie MeSH
- lidé MeSH
- nukleokapsida - proteiny MeSH
- Check Tag
- lidé MeSH
Morphine is considered a gold standard in pain treatment. Nevertheless, its use could be associated with severe side effects, including drug addiction. Thus, it is very important to understand the molecular mechanism of morphine action in order to develop new methods of pain therapy, or at least to attenuate the side effects of opioids usage. Proteomics allows for the indication of proteins involved in certain biological processes, but the number of items identified in a single study is usually overwhelming. Thus, researchers face the difficult problem of choosing the proteins which are really important for the investigated processes and worth further studies. Therefore, based on the 29 published articles, we created a database of proteins regulated by morphine administration - The Morphinome Database (addiction-proteomics.org). This web tool allows for indicating proteins that were identified during different proteomics studies. Moreover, the collection and organization of such a vast amount of data allows us to find the same proteins that were identified in various studies and to create their ranking, based on the frequency of their identification. STRING and KEGG databases indicated metabolic pathways which those molecules are involved in. This means that those molecular pathways seem to be strongly affected by morphine administration and could be important targets for further investigations. SIGNIFICANCE: The data about proteins identified by different proteomics studies of molecular changes caused by morphine administration (29 published articles) were gathered in the Morphinome Database. Unification of those data allowed for the identification of proteins that were indicated several times by distinct proteomics studies, which means that they seem to be very well verified and important for the entire process. Those proteins might be now considered promising aims for more detailed studies of their role in the molecular mechanism of morphine action.
Quaternary ammonium salts (QUATs) are compounds with wide use in organic synthesis, pharmacy or other fields of industry. Thanks to their specific physical and chemical properties resulting from their amphiphilic character they are already used as phase-transfer catalysts, ionic liquids, dyes, antimicrobial agents and disinfectants, antiarrhythmics, bronchodilators etc. There is still an effort to prepare new active compounds. Several organosynthetic methods are used to prepare QUATs: probably the best way is the Menshutkin reaction. Recently, also a microwave synthesis was introduced to prepare QUATs bringing better yields, shorter reaction times and a possibility of solvent-free reactions.
