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Antivirals and Antiviral Strategies
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Antivirals and Antiviral Strategies

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

Deadline for manuscript submissions: closed (31 March 2023) | Viewed by 13063

Special Issue Editor

Dr. Anna Shtro

E-Mail Website
Guest Editor
Laboratory of Antiviral Chemotherapy, Smorodintsev Research Institute of Influenza, 197376 Saint Petersburg, Russia
Interests: antivirals; chemotherapy; influenza; RSV; coronavirus; respiratory infections
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The Special Issue is devoted to novel antiviral agent research. We look forward to receiving articles on the following topics:

  1. Drug design and molecular modeling in silico;
  2. Antiviral activity of small molecules and protein or nucleic preparations in vitro;
  3. In vivo research of antivirals using animal models;
  4. Results of clinical and preclinical trials;
  5. Research showing a drug’s mechanism of action.

Paper selection will be carried out during the peer review process. Submitted papers must not be under consideration by another journal or publication.

Dr. Anna Shtro
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

  • antivirals
  • COVID-19
  • therapy strategies
  • antiviral drugs
  • small molecules
  • viral infections
  • chemotherapy

Published Papers (6 papers)

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Research

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13 pages, 2247 KiB  
Article
Bioassay-Guided Fractionation of Erythrostemon yucatanensis (Greenm.) Gagnon & GP Lewis Components with Anti-hemagglutinin Binding Activity against Influenza A/H1N1 Virus
by Tania Ortiz-López, Rocío Borges-Argáez, Guadalupe Ayora-Talavera, Ernesto Canto-Ramírez, Lisseth Cetina-Montejo, Ángel May-May, Fabiola Escalante-Erosa and Mirbella Cáceres-Farfán
Molecules 2022, 27(17), 5494; https://doi.org/10.3390/molecules27175494 - 26 Aug 2022
Cited by 3 | Viewed by 1283
Abstract
Erythrostemon yucatanensis (Greenm.) Gagnon & GP Lewis is a legume tree native to and widely distributed in southeast Mexico, where its branches are used in traditional medicine. An in vitro evaluation of the antiviral activity of extracts and fractions from the leaves, stem [...] Read more.
Erythrostemon yucatanensis (Greenm.) Gagnon & GP Lewis is a legume tree native to and widely distributed in southeast Mexico, where its branches are used in traditional medicine. An in vitro evaluation of the antiviral activity of extracts and fractions from the leaves, stem bark and roots against two strains of the AH1N1 influenza virus was performed, leading to the identification of bioactive compounds in this medicinal plant. In a cytopathic effect reduction assay, the fractions from the leaves and stem bark were the active elements at the co-treatment level. These were further fractionated based on their hemagglutination inhibition activity. The analysis of spectroscopy data identified a combination of phytosterols (β-sitosterol, stigmasterol and campesterol) in the stem bark active fraction as the main anti-hemagglutinin binding components, while 5-hydroxy-2(2-hydroxy-3,4,5-trimethoxyphenyl)-7-metoxi-4H(chromen-4-ona), which was isolated from the leaf extracts, showed a weak inhibition of viral hemagglutinin. Time of addition experiments demonstrated that the mixture of sterols had a direct effect on viral particle infectivity at the co-treatment level (IC50 = 3.125 µg/mL). This effect was also observed in the virus plaque formation inhibition assay, where the mixture showed 90% inhibition in the first 20 min of co-treatment at the same concentration. Additionally, it was found using qRT-PCR that the NP copy number was reduced by 92.85% after 60 min of co-treatment. These results are the first report of components with anti-hemagglutinin binding activity in the genus Erythrostemon sp. Full article
(This article belongs to the Special Issue Antivirals and Antiviral Strategies)
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21 pages, 2150 KiB  
Article
Synthesis and Antiviral Properties of Camphor-Derived Iminothiazolidine-4-Ones and 2,3-Dihydrothiazoles
by Vladislav V. Oreshko, Kseniya S. Kovaleva, Ekaterina D. Mordvinova, Olga I. Yarovaya, Yuri V. Gatilov, Dmitry N. Shcherbakov, Nikolai I. Bormotov, Olga A. Serova, Larisa N. Shishkina and Nariman F. Salakhutdinov
Molecules 2022, 27(15), 4761; https://doi.org/10.3390/molecules27154761 - 25 Jul 2022
Cited by 5 | Viewed by 1716
Abstract
A set of heterocyclic products was synthesized from natural (+)-camphor and semi-synthetic (−)-camphor. Then, 2-Imino-4-thiazolidinones and 2,3-dihydrothiazoles were obtained using a three-step procedure. For the synthesized compounds, their antiviral activity against the vaccinia virus and Marburg virus was studied. New promising agents active [...] Read more.
A set of heterocyclic products was synthesized from natural (+)-camphor and semi-synthetic (−)-camphor. Then, 2-Imino-4-thiazolidinones and 2,3-dihydrothiazoles were obtained using a three-step procedure. For the synthesized compounds, their antiviral activity against the vaccinia virus and Marburg virus was studied. New promising agents active against both viruses were found among the tested compounds. Full article
(This article belongs to the Special Issue Antivirals and Antiviral Strategies)
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Graphical abstract

12 pages, 1993 KiB  
Article
Andrographolide Inhibits Epstein–Barr Virus Lytic Reactivation in EBV-Positive Cancer Cell Lines through the Modulation of Epigenetic-Related Proteins
by Praphatson Malat, Tipaya Ekalaksananan, Chukkris Heawchaiyaphum, Supawadee Suebsasana, Sittiruk Roytrakul, Yodying Yingchutrakul and Chamsai Pientong
Molecules 2022, 27(14), 4666; https://doi.org/10.3390/molecules27144666 - 21 Jul 2022
Cited by 2 | Viewed by 1647
Abstract
Reactivation of Epstein–Barr virus (EBV) is associated with EBV-associated malignancies and is considered to be a benefit target for treatment. Andrographolide is claimed to have antiviral and anti-tumor activities. Therefore, this study aimed to investigate the effect of andrographolide on the inhibition of [...] Read more.
Reactivation of Epstein–Barr virus (EBV) is associated with EBV-associated malignancies and is considered to be a benefit target for treatment. Andrographolide is claimed to have antiviral and anti-tumor activities. Therefore, this study aimed to investigate the effect of andrographolide on the inhibition of EBV lytic reactivation in EBV-positive cancer cells. The cytotoxicity of andrographolide was firstly evaluated in EBV-positive cancer cells; P3HR1, AGS-EBV and HONE1-EBV cells, using an MTT assay. Herein, the spontaneous expression of EBV lytic genes; BALF5, BRLF1 and BZLF1, was significantly inhibited in andrographolide-treated cells. Accordingly, andrographolide inhibited the expression of Zta and viral production in sodium butyrate (NaB)-induced EBV lytic reactivation. Additionally, proteomics and bioinformatics analysis revealed the differentially expressed proteins that inhibit EBV lytic reactivation in all treated cell lines were functionally related with the histone modifications and chromatin organization, such as histone H3-K9 modification and histone H3-K27 methylation. Taken together, andrographolide inhibits EBV reactivation in EBV-positive cancer cells by inhibiting EBV lytic genes, probably, through the histone modifications. Full article
(This article belongs to the Special Issue Antivirals and Antiviral Strategies)
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16 pages, 3452 KiB  
Article
Styrylpyrone Derivative (SPD) Extracted from Goniothalamus umbrosus Binds to Dengue Virus Serotype-2 Envelope Protein and Inhibits Early Stage of Virus Replication
by Noor Zarina Abd Wahab and Nazlina Ibrahim
Molecules 2022, 27(14), 4566; https://doi.org/10.3390/molecules27144566 - 18 Jul 2022
Cited by 7 | Viewed by 1718
Abstract
A study was conducted to investigate the anti-viral effect of a styrylpyrone derivative (SPD) called goniothalamin and the effects on the dengue virus serotype 2 (DENV-2) replication cycle. The SPD was prepared from the root of Goniothalamus umbrosus after purification with petroleum ether. [...] Read more.
A study was conducted to investigate the anti-viral effect of a styrylpyrone derivative (SPD) called goniothalamin and the effects on the dengue virus serotype 2 (DENV-2) replication cycle. The SPD was prepared from the root of Goniothalamus umbrosus after purification with petroleum ether. The isolated SPD was then subjected to gas chromatography–mass spectrometry (GC-MS) and nuclear magnetic resonance (NMR) analyses for structure validation. The cytotoxicity of the SPD was evaluated using a cell viability assay, while the anti-viral activity of the SPD towards DENV-2 was confirmed by conducting a foci reduction assay which involved virus yield reduction, time-of-addition, and time removal assays. Transcriptomic analysis via quantitative real-time polymerase chain reaction (qRT-PCR) using the DENV-2 E gene was conducted to investigate the level of gene transcript. Immunocytochemistry analysis was used to investigate the effects of SPD treatment on protein E expression. Finally, software molecular docking of the SPD and E protein was also performed. The cytotoxicity assay confirmed that the SPD was not toxic to Vero cells, even at the highest concentration tested. In the time-of-addition assay, more than 80% foci reduction was observed when SPDs were administered at 2 h post-infection (hpi), and the reduction percentage then dropped with the delay of the treatment time, suggesting the inhibition of the early replication cycle. However, the time removal assay showed that more than 80% reduction could only be observed after 96 h post-treatment with the SPD. Treatment with the SPD reduced the progeny infectivity when treated for 24 h and was dose-dependent. The result showed that transcript level of the E gene in infected cells treated with the SPD was reduced compared to infected cells without treatment. In immunocytochemistry analysis, the DENV-2 E protein exhibited similar expression trends, shown by the gene transcription level. Molecular docking showed that the SPD can interact with E protein through hydrogen bonds and other interactions. Overall, this study showed that SPDs have the potential to be anti-DENV-2 via a reduction in viral progeny infectivity and a reduction in the expression of the DENV-2 E gene and protein at different phases of viral replication. SPDs should be further researched to be developed into an effective anti-viral treatment, particularly for early-phase dengue viral infection. Full article
(This article belongs to the Special Issue Antivirals and Antiviral Strategies)
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Review

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27 pages, 910 KiB  
Review
Microbial Natural Products with Antiviral Activities, Including Anti-SARS-CoV-2: A Review
by Andri Frediansyah, Fajar Sofyantoro, Saad Alhumaid, Abbas Al Mutair, Hawra Albayat, Hayyan I. Altaweil, Hani M. Al-Afghani, Abdullah A. AlRamadhan, Mariam R. AlGhazal, Safaa A. Turkistani, Abdulmonem A. Abuzaid and Ali A. Rabaan
Molecules 2022, 27(13), 4305; https://doi.org/10.3390/molecules27134305 - 05 Jul 2022
Cited by 10 | Viewed by 3867
Abstract
The SARS-CoV-2 virus, which caused the COVID-19 infection, was discovered two and a half years ago. It caused a global pandemic, resulting in millions of deaths and substantial damage to the worldwide economy. Currently, only a few vaccines and antiviral drugs are available [...] Read more.
The SARS-CoV-2 virus, which caused the COVID-19 infection, was discovered two and a half years ago. It caused a global pandemic, resulting in millions of deaths and substantial damage to the worldwide economy. Currently, only a few vaccines and antiviral drugs are available to combat SARS-CoV-2. However, there has been an increase in virus-related research, including exploring new drugs and their repurposing. Since discovering penicillin, natural products, particularly those derived from microbes, have been viewed as an abundant source of lead compounds for drug discovery. These compounds treat bacterial, fungal, parasitic, and viral infections. This review incorporates evidence from the available research publications on isolated and identified natural products derived from microbes with anti-hepatitis, anti-herpes simplex, anti-HIV, anti-influenza, anti-respiratory syncytial virus, and anti-SARS-CoV-2 properties. About 131 compounds with in vitro antiviral activity and 1 compound with both in vitro and in vivo activity have been isolated from microorganisms, and the mechanism of action for some of these compounds has been described. Recent reports have shown that natural products produced by the microbes, such as aurasperone A, neochinulin A and B, and aspulvinone D, M, and R, have potent in vitro anti-SARS-CoV-2 activity, targeting the main protease (Mpro). In the near and distant future, these molecules could be used to develop antiviral drugs for treating infections and preventing the spread of disease. Full article
(This article belongs to the Special Issue Antivirals and Antiviral Strategies)
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12 pages, 275 KiB  
Review
Protein and Peptide Substances in the Treatment of Respiratory Syncytial Infection: Current State
by Anna A. Shtro, Galina D. Petukhova and Aleksandra S. Romanova
Molecules 2022, 27(7), 2263; https://doi.org/10.3390/molecules27072263 - 31 Mar 2022
Cited by 4 | Viewed by 1943
Abstract
Respiratory syncytial virus infection (RSVI) is an acute medical and social problem in many countries globally. Infection is most dangerous for infants under one year old and the elderly. Despite its epidemiological relevance, only two drugs are registered for clinical use against RSVI: [...] Read more.
Respiratory syncytial virus infection (RSVI) is an acute medical and social problem in many countries globally. Infection is most dangerous for infants under one year old and the elderly. Despite its epidemiological relevance, only two drugs are registered for clinical use against RSVI: ribavirin (approved in a limited number of countries due to side effects) and palivizumab (Synagis), which is intended only for the prevention, but not the treatment, of infection. Currently, various research groups are searching for new drugs against RSV, with three main areas of research: small molecules, polymeric drugs (proteins and peptides), and plant extracts. This review is devoted to currently developed protein and peptide anti-RSV drugs. Full article
(This article belongs to the Special Issue Antivirals and Antiviral Strategies)
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