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Current Advances in Novel Antiviral Drugs
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Current Advances in Novel Antiviral Drugs

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pharmacology".

Deadline for manuscript submissions: closed (20 September 2024) | Viewed by 4237

Special Issue Editor

Dr. Alexey V. Ustinov

E-Mail Website1 Website2
Guest Editor
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, Russia
Interests: antiviral research; organic synthesis; molecular design

Special Issue Information

Dear Colleagues,

The advances of modern transportation contribute greatly to the worldwide dissemination of viral pathogens that used to be confined to local areas, leading to the promotion of local outbreaks into full-blown pandemics. The emergence of COVID-19 is the first example of such an event in human history, but likely not the last. The rapid evolution and genetic variability of viral diseases are expected to continue challenging worldwide healthcare with new types of assaults.

The development of antiviral strategies targeting a wide range of potential pathogens is thus necessary as the first line of preparation against these new challenges. The putative targets for broad-spectrum antivirals include, but are not limited to, lipid membranes of the viral envelopes, broad targets of nucleic acid metabolism and replication, and enzymatic machinery responsible for virion assembly, fusion, and budding. This Special Issue is thus focused on recent advances in the development of molecules with the potential for broad antiviral action.

Dr. Alexey V. Ustinov
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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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

  • broad-spectrum antivirals
  • antiviral mechanisms
  • non-nucleoside antivirals
  • antiviral resistance
  • emerging viruses

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Published Papers (2 papers)

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Research

37 pages, 7557 KiB  
Article
Alkyl Derivatives of Perylene Photosensitizing Antivirals: Towards Understanding the Influence of Lipophilicity
by Igor E. Mikhnovets, Jiří Holoubek, Irina S. Panina, Jan Kotouček, Daniil A. Gvozdev, Stepan P. Chumakov, Maxim S. Krasilnikov, Mikhail Y. Zhitlov, Evgeny L. Gulyak, Alexey A. Chistov, Timofei D. Nikitin, Vladimir A. Korshun, Roman G. Efremov, Vera A. Alferova, Daniel Růžek, Luděk Eyer and Alexey V. Ustinov
Int. J. Mol. Sci. 2023, 24(22), 16483; https://doi.org/10.3390/ijms242216483 - 18 Nov 2023
Cited by 1 | Viewed by 1939
Abstract
Amphipathic perylene derivatives are broad-spectrum antivirals against enveloped viruses that act as fusion inhibitors in a light-dependent manner. The compounds target the lipid bilayer of the viral envelope using the lipophilic perylene moiety and photogenerating singlet oxygen, thereby causing damage to unsaturated lipids. [...] Read more.
Amphipathic perylene derivatives are broad-spectrum antivirals against enveloped viruses that act as fusion inhibitors in a light-dependent manner. The compounds target the lipid bilayer of the viral envelope using the lipophilic perylene moiety and photogenerating singlet oxygen, thereby causing damage to unsaturated lipids. Previous studies show that variation of the polar part of the molecule is important for antiviral activity. Here, we report modification of the lipophilic part of the molecule, perylene, by the introduction of 4-, 8-, and 12-carbon alkyls into position 9(10) of the perylene residue. Using Friedel–Crafts acylation and Wolff–Kishner reduction, three 3-acetyl-9(10)-alkylperylenes were synthesized from perylene and used to prepare 9 nucleoside and 12 non-nucleoside amphipathic derivatives. These compounds were characterized as fluorophores and singlet oxygen generators, as well as tested as antivirals against herpes virus-1 (HSV-1) and vesicular stomatitis virus (VSV), both known for causing superficial skin/mucosa lesions and thus serving as suitable candidates for photodynamic therapy. The results suggest that derivatives with a short alkyl chain (butyl) have strong antiviral activity, whereas the introduction of longer alkyl substituents (n = 8 and 12) to the perylenyethynyl scaffold results in a dramatic reduction of antiviral activity. This phenomenon is likely attributable to the increased lipophilicity of the compounds and their ability to form insoluble aggregates. Moreover, molecular dynamic studies revealed that alkylated perylene derivatives are predominately located closer to the middle of the bilayer compared to non-alkylated derivatives. The predicted probability of superficial positioning correlated with antiviral activity, suggesting that singlet oxygen generation is achieved in the subsurface layer of the membrane, where the perylene group is more accessible to dissolved oxygen. Full article
(This article belongs to the Special Issue Current Advances in Novel Antiviral Drugs)
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18 pages, 1992 KiB  
Article
Phenotypic Test of Benzo[4,5]imidazo[1,2-c]pyrimidinone-Based Nucleoside and Non-Nucleoside Derivatives against DNA and RNA Viruses, Including Coronaviruses
by Polina Kamzeeva, Ivan Petushkov, Ekaterina Knizhnik, Robert Snoeck, Yuri Khodarovich, Ekaterina Ryabukhina, Vera Alferova, Artur Eshtukov-Shcheglov, Evgeny Belyaev, Julia Svetlova, Tatiana Vedekhina, Andrey Kulbachinskiy, Anna Varizhuk, Graciela Andrei and Andrey Aralov
Int. J. Mol. Sci. 2023, 24(19), 14540; https://doi.org/10.3390/ijms241914540 - 26 Sep 2023
Viewed by 1677
Abstract
Emerging and re-emerging viruses periodically cause outbreaks and epidemics around the world, which ultimately lead to global events such as the COVID-19 pandemic. Thus, the urgent need for new antiviral drugs is obvious. Over more than a century of antiviral development, nucleoside analogs [...] Read more.
Emerging and re-emerging viruses periodically cause outbreaks and epidemics around the world, which ultimately lead to global events such as the COVID-19 pandemic. Thus, the urgent need for new antiviral drugs is obvious. Over more than a century of antiviral development, nucleoside analogs have proven to be promising agents against diversified DNA and RNA viruses. Here, we present the synthesis and evaluation of the antiviral activity of nucleoside analogs and their deglycosylated derivatives based on a hydroxybenzo[4,5]imidazo[1,2-c]pyrimidin-1(2H)-one scaffold. The antiviral activity was evaluated against a panel of structurally and phylogenetically diverse RNA and DNA viruses. The leader compound showed micromolar activity against representatives of the family Coronaviridae, including SARS-CoV-2, as well as against respiratory syncytial virus in a submicromolar range without noticeable toxicity for the host cells. Surprisingly, methylation of the aromatic hydroxyl group of the leader compound resulted in micromolar activity against the varicella-zoster virus without any significant impact on cell viability. The leader compound was shown to be a weak inhibitor of the SARS-CoV-2 RNA-dependent RNA polymerase. It also inhibited biocondensate formation important for SARS-CoV-2 replication. The active compounds may be considered as a good starting point for further structure optimization and mechanistic and preclinical studies. Full article
(This article belongs to the Special Issue Current Advances in Novel Antiviral Drugs)
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