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Microorganisms
Special Issues
Antiviral Drug Discovery and Development in the Twenty-First Century
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Antiviral Drug Discovery and Development in the Twenty-First Century

A special issue of Microorganisms (ISSN 2076-2607). This special issue belongs to the section "Antimicrobial Agents and Resistance".

Deadline for manuscript submissions: closed (31 December 2020) | Viewed by 25002

Special Issue Editor

Dr. Javier Sanchez-Cespedes

E-Mail Website
Guest Editor
Clinical Unit of Infectious Diseases, Microbiology, and Preventive Medicine, Infectious Diseases Research Group, University Hospital Virgen del Rocío/Institute of Biomedicine of Seville (IBiS)/University of Seville/CSIC, Seville, Spain
Interests: adenovirus (HAdV); DNA viruses; infectious diseases; antiviral drug discovery and development; synthetic compounds; natural products; virology; pharmacology; medicinal chemistry

Special Issue Information

Dear Colleagues,

Epidemics of emerging and re-emerging viral diseases pose a real threat to global health. Most of viruses lack adequate drugs for their treatment and eradication including SARS-CoV-2, Ebola virus, Zika virus, MERS-CoV, dengue virus, or human adenovirus (HAdV) and herpes viruses, the last two affecting immunosuppressed patients mainly. Moreover, the use of the currently available antivirals is often limited by their toxicity and the emergence of viral resistance. In this context, the World Health Organization (WHO) highlights the critical need to prepare for epidemics and bolster our arsenal for stopping infectious diseases (https://www.who.int/).

This lack of adequate treatments constitutes an important health and economic problem and is of acute relevance during emerging outbreaks and also in certain patient populations such as those in transplantation programs which suffer a high rate of disease and transplant failure associated with viral infections.

Next generation sequencing, CRISPR based-approaches or imaging technologies are transforming medical sciences, including the antivirals field. In addition, genomics and proteomics are helping in the identification of host factors as new targets for drug development. The availability of these new tools should help to enhance the development of new families of antiviral drugs addressing the wide number of unmet medical needs in viral diseases.

Dr. Javier Sanchez-Cespedes
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. Microorganisms is an international peer-reviewed open access monthly 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

  • virology
  • drug development
  • virus-host interactions
  • medicinal chemistry

Published Papers (5 papers)

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Research

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10 pages, 2034 KiB  
Article
Antiviral Activity of Vacuolar ATPase Blocker Diphyllin against SARS-CoV-2
by Michal Stefanik, Petra Strakova, Jan Haviernik, Andrew D. Miller, Daniel Ruzek and Ludek Eyer
Microorganisms 2021, 9(3), 471; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms9030471 - 25 Feb 2021
Cited by 15 | Viewed by 3611
Abstract
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a causative agent of the pandemic coronavirus disease 2019 (COVID-19), which has resulted in over two million deaths worldwide to date. Diphyllin and diphyllinosides are known as natural blockers of cellular vacuolar ATPases, and so [...] Read more.
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a causative agent of the pandemic coronavirus disease 2019 (COVID-19), which has resulted in over two million deaths worldwide to date. Diphyllin and diphyllinosides are known as natural blockers of cellular vacuolar ATPases, and so can act as inhibitors of the pH-dependent fusion of viral envelopes with host cell endosomal membranes. Such pH-dependent fusion is a critical early step during the SARS-CoV-2 replication cycle. Accordingly, the anti-SARS-CoV-2 profiles and cytotoxicities of diphyllin, diphyllinoside cleistanthin B, and two structurally related compounds, helioxanthin 8-1 and helioxanthin 5-4-2, are evaluated here using in vitro cell-based assay systems. Neither helioxanthin exhibits any obvious anti-SARS-CoV-2 effects in vitro. By contrast diphyllin and cleistanthin B do exhibit anti-SARS-CoV-2 effects in Vero cells, with respective 50% effective concentrations (EC50) values of 1.92 and 6.51 µM. Diphyllin displays anti-SARS-CoV-2 effect also in colorectal adenocarcinoma (CaCo-2) cells. Moreover, when diphyllin is added at various times post infection, a significant decrease in viral titer is observed in SARS-CoV-2-infected Vero cells, even at high viral multiplicities of infection. Importantly, neither diphyllin nor cleistanthin B are found cytotoxic to Vero cells in concentrations up to 100 µM. However, the cytotoxic effect of diphyllin is more pronounced in Vero E6 and CaCo-2 cells. Overall, our data demonstrate that diphyllin and diphyllin analogues might be perfected as anti-SARS-CoV-2 agents in future preclinical studies, most especially if nanomedicine approaches may be invoked to optimize functional drug delivery to virus infected cells. Full article
(This article belongs to the Special Issue Antiviral Drug Discovery and Development in the Twenty-First Century)
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16 pages, 2327 KiB  
Article
Antiviral Effects of Curcumin on Adenovirus Replication
by Morgan R. Jennings and Robin J. Parks
Microorganisms 2020, 8(10), 1524; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms8101524 - 04 Oct 2020
Cited by 9 | Viewed by 2616
Abstract
Human adenovirus (HAdV) is a common pathogen that can cause severe morbidity and mortality in certain populations, including pediatric, geriatric, and immunocompromised patients. Unfortunately, there are no approved therapeutics to combat HAdV infections. Curcumin, the primary curcuminoid compound found in turmeric spice, has [...] Read more.
Human adenovirus (HAdV) is a common pathogen that can cause severe morbidity and mortality in certain populations, including pediatric, geriatric, and immunocompromised patients. Unfortunately, there are no approved therapeutics to combat HAdV infections. Curcumin, the primary curcuminoid compound found in turmeric spice, has shown broad activity as an antimicrobial agent, limiting the replication of many different bacteria and viruses. In this study, we evaluated curcumin as an anti-HAdV agent. Treatment of cells in culture with curcumin reduced HAdV replication, gene expression, and virus yield, at concentrations of curcumin that had little effect on cell viability. Thus, curcumin represents a promising class of compounds for further study as potential therapeutics to combat HAdV infection. Full article
(This article belongs to the Special Issue Antiviral Drug Discovery and Development in the Twenty-First Century)
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Review

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19 pages, 2463 KiB  
Review
Targeting the DEAD-Box RNA Helicase eIF4A with Rocaglates—A Pan-Antiviral Strategy for Minimizing the Impact of Future RNA Virus Pandemics
by Gaspar Taroncher-Oldenburg, Christin Müller, Wiebke Obermann, John Ziebuhr, Roland K. Hartmann and Arnold Grünweller
Microorganisms 2021, 9(3), 540; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms9030540 - 05 Mar 2021
Cited by 14 | Viewed by 4877
Abstract
The increase in pandemics caused by RNA viruses of zoonotic origin highlights the urgent need for broad-spectrum antivirals against novel and re-emerging RNA viruses. Broad-spectrum antivirals could be deployed as first-line interventions during an outbreak while virus-specific drugs and vaccines are developed and [...] Read more.
The increase in pandemics caused by RNA viruses of zoonotic origin highlights the urgent need for broad-spectrum antivirals against novel and re-emerging RNA viruses. Broad-spectrum antivirals could be deployed as first-line interventions during an outbreak while virus-specific drugs and vaccines are developed and rolled out. Viruses depend on the host’s protein synthesis machinery for replication. Several natural compounds that target the cellular DEAD-box RNA helicase eIF4A, a key component of the eukaryotic translation initiation complex eIF4F, have emerged as potential broad-spectrum antivirals. Rocaglates, a group of flavaglines of plant origin that clamp mRNAs with highly structured 5′ untranslated regions (5′UTRs) onto the surface of eIF4A through specific stacking interactions, exhibit the largest selectivity and potential therapeutic indices among all known eIF4A inhibitors. Their unique mechanism of action limits the inhibitory effect of rocaglates to the translation of eIF4A-dependent viral mRNAs and a minor fraction of host mRNAs exhibiting stable RNA secondary structures and/or polypurine sequence stretches in their 5′UTRs, resulting in minimal potential toxic side effects. Maintaining a favorable safety profile while inducing efficient inhibition of a broad spectrum of RNA viruses makes rocaglates into primary candidates for further development as pan-antiviral therapeutics. Full article
(This article belongs to the Special Issue Antiviral Drug Discovery and Development in the Twenty-First Century)
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20 pages, 912 KiB  
Review
Recent Advances in Novel Antiviral Therapies against Human Adenovirus
by Bratati Saha and Robin J. Parks
Microorganisms 2020, 8(9), 1284; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms8091284 - 22 Aug 2020
Cited by 16 | Viewed by 3880
Abstract
Human adenovirus (HAdV) is a very common pathogen that typically causes minor disease in most patients. However, the virus can cause significant morbidity and mortality in certain populations, including young children, the elderly, and those with compromised immune systems. Currently, there are no [...] Read more.
Human adenovirus (HAdV) is a very common pathogen that typically causes minor disease in most patients. However, the virus can cause significant morbidity and mortality in certain populations, including young children, the elderly, and those with compromised immune systems. Currently, there are no approved therapeutics to treat HAdV infections, and the standard treatment relies on drugs approved to combat other viral infections. Such treatments often show inconsistent efficacy, and therefore, more effective antiviral therapies are necessary. In this review, we discuss recent developments in the search for new chemical and biological anti-HAdV therapeutics, including drugs that are currently undergoing preclinical/clinical testing, and small molecule screens for the identification of novel compounds that abrogate HAdV replication and disease. Full article
(This article belongs to the Special Issue Antiviral Drug Discovery and Development in the Twenty-First Century)
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18 pages, 1736 KiB  
Review
Progress in Developing Inhibitors of SARS-CoV-2 3C-Like Protease
by Qingxin Li and CongBao Kang
Microorganisms 2020, 8(8), 1250; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms8081250 - 18 Aug 2020
Cited by 87 | Viewed by 9216
Abstract
Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The viral outbreak started in late 2019 and rapidly became a serious health threat to the global population. COVID-19 was declared a pandemic by the World Health Organization in [...] Read more.
Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The viral outbreak started in late 2019 and rapidly became a serious health threat to the global population. COVID-19 was declared a pandemic by the World Health Organization in March 2020. Several therapeutic options have been adopted to prevent the spread of the virus. Although vaccines have been developed, antivirals are still needed to combat the infection of this virus. SARS-CoV-2 is an enveloped virus, and its genome encodes polyproteins that can be processed into structural and nonstructural proteins. Maturation of viral proteins requires cleavages by proteases. Therefore, the main protease (3 chymotrypsin-like protease (3CLpro) or Mpro) encoded by the viral genome is an attractive drug target because it plays an important role in cleaving viral polyproteins into functional proteins. Inhibiting this enzyme is an efficient strategy to block viral replication. Structural studies provide valuable insight into the function of this protease and structural basis for rational inhibitor design. In this review, we describe structural studies on the main protease of SARS-CoV-2. The strategies applied in developing inhibitors of the main protease of SARS-CoV-2 and currently available protein inhibitors are summarized. Due to the availability of high-resolution structures, structure-guided drug design will play an important role in developing antivirals. The availability of high-resolution structures, potent peptidic inhibitors, and diverse compound scaffolds indicate the feasibility of developing potent protease inhibitors as antivirals for COVID-19. Full article
(This article belongs to the Special Issue Antiviral Drug Discovery and Development in the Twenty-First Century)
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