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Novel COVID-Related Anti-inflammatory Drugs
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Novel COVID-Related Anti-inflammatory Drugs

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Medicinal Chemistry".

Deadline for manuscript submissions: closed (31 October 2022) | Viewed by 6838

Special Issue Editor

Prof. Dr. Christian Lehmann

E-Mail Website
Guest Editor
Department of Anesthesiology, Dalhousie University, Halifax, NS, Canada
Interests: cannabinoids; infection; sepsis and its early indications; intravital imaging microcirculation; septic shock stroke
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The COVID-19 pandemic will continue to infect a large portion of the world’s population and cause substantial morbidity and mortality until either an effective vaccine or a useful antiviral therapeutic is developed. To date, potential vaccines have a long lead time, and their potential efficacy is uncertain given past failures with coronavirus vaccines. Furthermore, there is no approved antiviral therapy for COVID-19 infection. Therefore, alternative approaches must be explored in the hope of diminishing the potential consequences of COVID-19. Since many patients with COVID-19 show a massive cytokine release ("cytokine storm"), anti-inflammatory drugs have been suggested as potential treatments. This Special Issue of Molecules focuses on anti-inflammatory approaches to treat the immune dysregulation in COVID-19.

Prof. Dr. Christian Lehmann
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Molecules is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • SARS-CoV-2
  • COVID-19
  • infection
  • inflammation
  • cytokines
  • anti-inflammatory drugs

Published Papers (3 papers)

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Research

16 pages, 7425 KiB  
Article
Amino Derivatives of Diaryl Pyrimidines and Azolopyrimidines as Protective Agents against LPS-Induced Acute Lung Injury
by Alexander Spasov, Irina Ovchinnikova, Olga Fedorova, Yulia Titova, Denis Babkov, Vadim Kosolapov, Alexander Borisov, Elena Sokolova, Vladlen Klochkov, Maria Skripka, Yulia Velikorodnaya, Alexey Smirnov, Gennady Rusinov and Valery Charushin
Molecules 2023, 28(2), 741; https://doi.org/10.3390/molecules28020741 - 11 Jan 2023
Cited by 1 | Viewed by 1503
Abstract
The problem of lung damage originating from excessive inflammation and cytokine release during various types of infections remains relevant and stimulates the search for highly effective and safe drugs. The biological activity of the latter may be associated with the regulation of hyperactivation [...] Read more.
The problem of lung damage originating from excessive inflammation and cytokine release during various types of infections remains relevant and stimulates the search for highly effective and safe drugs. The biological activity of the latter may be associated with the regulation of hyperactivation of certain immune cells and enzymes. Here, we propose the design and synthesis of amino derivatives of 4,6- and 5,7-diaryl substituted pyrimidines and [1,2,4]triazolo[1,5-a]pyrimidines as promising double-acting pharmacophores inhibiting IL-6 and NO. The anti-inflammatory activity of 14 target compounds was studied on isolated primary murine macrophages after LPS stimulation. Seven compounds were identified to inhibit the synthesis of nitric oxide and interleukin 6 at a concentration of 100 µM. The most active compounds are micromolar inhibitors of IL-6 secretion and NO synthesis, showing a minimal impact on innate immunity, unlike the reference drug dexamethasone, along with acceptable cytotoxicity. Evaluation in an animal model of acute lung injury proved the protective activity of compound 6e, which was supported by biochemical, cytological and morphological markers. Full article
(This article belongs to the Special Issue Novel COVID-Related Anti-inflammatory Drugs)
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13 pages, 2808 KiB  
Article
Anti-Inflammatory Effects of the Iron Chelator, DIBI, in Experimental Acute Lung Injury
by Christian Lehmann, Nazli Alizadeh-Tabrizi, Stefan Hall, Sufyan Faridi, Irene Euodia, Bruce Holbein, Juan Zhou and Valerie Chappe
Molecules 2022, 27(13), 4036; https://doi.org/10.3390/molecules27134036 - 23 Jun 2022
Cited by 4 | Viewed by 1818
Abstract
Iron plays a critical role in the immune response to inflammation and infection due to its role in the catalysis of reactive oxygen species (ROS) through the Haber-Weiss and Fenton reactions. However, ROS overproduction can be harmful and damage healthy cells. Therefore, iron [...] Read more.
Iron plays a critical role in the immune response to inflammation and infection due to its role in the catalysis of reactive oxygen species (ROS) through the Haber-Weiss and Fenton reactions. However, ROS overproduction can be harmful and damage healthy cells. Therefore, iron chelation represents an innovative pharmacological approach to limit excess ROS formation and the related pro-inflammatory mediator cascades. The present study was designed to investigate the impact of the iron chelator, DIBI, in an experimental model of LPS-induced acute lung injury (ALI). DIBI was administered intraperitoneally in the early and later stages of lung inflammation as determined by histopathological evaluation. We found that lung tissues showed significant injury, as well as increased NF-κB p65 activation and significantly elevated levels of various inflammatory mediators (LIX, CXCL2, CCL5, CXCL10, IL-1𝛽, IL-6) 4 h post ALI induction by LPS. Mice treated with DIBI (80 mg/kg) in the early stages (0 to 2 h) after LPS administration demonstrated a significant reduction of the histopathological damage score, reduced levels of NF-κB p65 activation, and reduced levels of inflammatory mediators. Intravital microscopy of the pulmonary microcirculation also showed a reduced number of adhering leukocytes and improved capillary perfusion with DIBI administration. Our findings support the conclusion that the iron chelator, DIBI, has beneficial anti-inflammatory effects in experimental ALI. Full article
(This article belongs to the Special Issue Novel COVID-Related Anti-inflammatory Drugs)
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13 pages, 2111 KiB  
Communication
Chlorpromazine, a Clinically Approved Drug, Inhibits SARS-CoV-2 Nucleocapsid-Mediated Induction of IL-6 in Human Monocytes
by Iwona Karwaciak, Kaja Karaś, Anna Sałkowska, Joanna Pastwińska and Marcin Ratajewski
Molecules 2022, 27(12), 3651; https://doi.org/10.3390/molecules27123651 - 07 Jun 2022
Cited by 7 | Viewed by 3095
Abstract
The COVID-19 pandemic, caused by the rapidly spreading SARS-CoV-2 virus, led to the unprecedented mobilization of scientists, resulting in the rapid development of vaccines and potential pharmaceuticals. Although COVID-19 symptoms are moderately severe in most people, in some cases the disease can result [...] Read more.
The COVID-19 pandemic, caused by the rapidly spreading SARS-CoV-2 virus, led to the unprecedented mobilization of scientists, resulting in the rapid development of vaccines and potential pharmaceuticals. Although COVID-19 symptoms are moderately severe in most people, in some cases the disease can result in pneumonia and acute respiratory failure as well as can be fatal. The severe course of COVID-19 is associated with a hyperinflammatory state called a cytokine storm. One of the key cytokines creating a proinflammatory environment is IL-6, which is secreted mainly by monocytes and macrophages. Therefore, this cytokine has become a target for some therapies that inhibit its biological action; however, these therapies are expensive, and their availability is limited in poorer countries. Thus, new cheaper drugs that can overcome the severe infections of COVID-19 are needed. Here, we show that chlorpromazine inhibits the expression and secretion of IL-6 by monocytes activated by SARS-CoV-2 virus nucleocapsid protein and affects the activity of NF-κB and MEK/ERK signaling. Our results, including others, indicate that chlorpromazine, which has been used for several decades as a neuroleptic, exerts antiviral and immunomodulatory activity, is safe and inexpensive, and might be a desirable drug to support the therapy of patients with COVID-19. Full article
(This article belongs to the Special Issue Novel COVID-Related Anti-inflammatory Drugs)
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