Novel and Repurposed Antiviral Agents

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Viral Immunology, Vaccines, and Antivirals".

Deadline for manuscript submissions: closed (16 December 2023) | Viewed by 9122

Special Issue Editors


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Guest Editor
Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung 404328, Taiwan
Interests: viral pathogenesis; antiviral agents; viral diagnosis
Special Issues, Collections and Topics in MDPI journals

E-Mail Website
Guest Editor
Department of Biotechnology and Laboratory Science in Medicine, National Yang Ming University, Taipei 112304, Taiwan
Interests: viral pathogenesis and immunology; enterovirus; antiviral agents
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The global outbreak of COVID-19 represents a significant threat for humanity. It is therefore an urgent and unmet need to search for antiviral therapeutics to fight against SARS-CoV-2. Re-positioning existing antiviral agents and screening their broad-spectrum antiviral activity against SARS-CoV-2 is pivotal. In addition to COVID-19, many epidemic viral diseases, such as influenza, dengue, Zika, Ebola, and Western/Eastern equine encephalitis, do not yet have effective therapies. Therefore, there are very few currently available drugs to control such virulent virus infections.

Developing novel and repurposed antiviral agents is a priority for treating epidemic diseases of emerging and re-emerging viruses. Targeting viral infectivity and modulating host defense systems are recognized as the main approaches to develop direct-acting antivirals (DAAs) and host-targeting agents (HTAs). The antiviral mechanisms of antiviral candidates should be deeply analyzed among different types of viral diseases. This Special Issue will serve as a platform for the study of DAAs and HTAs, facilitating the re-positioning of existing agents, herbal components, synthesized compounds, and genetic engineering molecules. We aim to explore the abilities of repurposed antiviral agents in the hope that they may become more promising for controlling future viral epidemics.

Prof. Dr. Cheng-Wen Lin
Dr. Szu-Hao Kung
Guest Editors

Manuscript Submission Information

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Keywords

  • antiviral agent
  • repurposed drug
  • emerging virus
  • direct-acting antiviral
  • host-targeting agent
  • molecular mechanism

Published Papers (5 papers)

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Research

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15 pages, 1126 KiB  
Article
Rosuvastatin as a Supplemental Treatment for the Clinical Symptoms of Nephropathia Epidemica: A Pilot Clinical Study
by Venera Shakirova, Maria Markelova, Yuriy Davidyuk, Robert J. Stott-Marshall, Toshana L. Foster, Svetlana Khaiboullina, Albert Rizvanov and Ekaterina Martynova
Viruses 2024, 16(2), 306; https://doi.org/10.3390/v16020306 - 17 Feb 2024
Viewed by 749
Abstract
Nephropathis epidemica (NE), a mild form of hemorrhagic fever with renal syndrome (HFRS), is an acute zoonotic disease endemic in the Republic of Tatarstan. This study aimed to assess the impact of rosuvastatin on the clinical and laboratory results of NE. A total [...] Read more.
Nephropathis epidemica (NE), a mild form of hemorrhagic fever with renal syndrome (HFRS), is an acute zoonotic disease endemic in the Republic of Tatarstan. This study aimed to assess the impact of rosuvastatin on the clinical and laboratory results of NE. A total of 61 NE patients and 30 controls were included in this study; 22 NE patients and 7 controls received a daily dose of rosuvastatin (10 mg) for ten consecutive days. Serum samples were collected on days 1, 5, and 10 after admission to the hospital. These samples were analyzed to determine the levels of lipids, cytokines, and kidney toxicity markers. Our findings indicate that rosuvastatin reduced the duration of the second wave of fever and alleviated back pain and headache symptoms. Additionally, low-density lipoprotein cholesterol (LDL-C) serum levels were significantly decreased on days 5 and 10 upon rosuvastatin treatment. Furthermore, rosuvastatin decreased the levels of cytokines in the serum, particularly proinflammatory cytokines IL-1β and IL-8. NE patients had significantly altered levels of the kidney toxicity markers albumin and osteopontin. The data from our study provide evidence supporting the therapeutic potential of rosuvastatin in NE cases. Full article
(This article belongs to the Special Issue Novel and Repurposed Antiviral Agents)
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15 pages, 3496 KiB  
Article
Novel Potent Autophagy Inhibitor Ka-003 Inhibits Dengue Virus Replication
by Jitra Limthongkul, Kornkamon Akkarasereenon, Tanpitcha Yodweerapong, Poramate Songthammawat, Pirut Tong-Ngam, Alisa Tubsuwan, Nawapol Kunkaew, Phongthon Kanjanasirirat, Tanawadee Khumpanied, Warawuth Wannalo, Sukathida Ubol, Suparerk Borwornpinyo, Poonsakdi Ploypradith and Marisa Ponpuak
Viruses 2023, 15(10), 2012; https://doi.org/10.3390/v15102012 - 27 Sep 2023
Viewed by 1410
Abstract
Every year, dengue virus (DENV) affects millions of people. Currently, there are no approved drugs for the treatment of DENV infection. Autophagy is a conserved degradation process that was shown to be induced by DENV infection and required for optimal DENV replication. The [...] Read more.
Every year, dengue virus (DENV) affects millions of people. Currently, there are no approved drugs for the treatment of DENV infection. Autophagy is a conserved degradation process that was shown to be induced by DENV infection and required for optimal DENV replication. The modulation of autophagy is, therefore, considered an attractive target to treat DENV infection. This study carried out a high-content image screen analysis using Crispr-Cas9 GFP-LC3 knocked-in HeLa cells of a compound library synthesized from or inspired by natural products and their biocongener precursors to discover novel autophagy inhibitors. The screen identified Ka-003 as the most effective compound for decreasing the number of autophagic vacuoles inside cells upon autophagy induction. Ka-003 could inhibit autophagy in a dose-dependent manner at low micromolar concentrations. More importantly, Ka-003 demonstrated the concentration-dependent inhibition of DENV production in Crispr-Cas9 GFP-LC3 knocked-in THP-1 monocytes. The core structure of Ka-003, which is a methyl cyclohexene derivative, resembles those found in mulberry plants, and could be synthetically prepared in a bioinspired fashion. Taken together, data indicate that Ka-003 hampered autophagy and limited DENV replication. The low cytotoxicity of Ka-003 suggests its therapeutic potential, which warrants further studies for the lead optimization of the compound for dengue treatment. Full article
(This article belongs to the Special Issue Novel and Repurposed Antiviral Agents)
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12 pages, 1180 KiB  
Article
Oral Probenecid for Nonhospitalized Adults with Symptomatic Mild-to-Moderate COVID-19
by David E. Martin, Neelam Pandey, Purvi Chavda, Gurpreet Singh, Rakesh Sutariya, Frederic Sancilio and Ralph A. Tripp
Viruses 2023, 15(7), 1508; https://doi.org/10.3390/v15071508 - 6 Jul 2023
Cited by 3 | Viewed by 3616
Abstract
Probenecid is an orally bioavailable, uricosuric agent that was first approved in 1951 for the treatment of gout, but was later found to have potent, broad-spectrum antiviral activity against several respiratory viruses including SARS-CoV-2. We conducted a phase 2 randomized, placebo-controlled, single-blind, dose-range [...] Read more.
Probenecid is an orally bioavailable, uricosuric agent that was first approved in 1951 for the treatment of gout, but was later found to have potent, broad-spectrum antiviral activity against several respiratory viruses including SARS-CoV-2. We conducted a phase 2 randomized, placebo-controlled, single-blind, dose-range finding study in non-hospitalized patients with symptomatic, mild-to-moderate COVID-19. Patients were randomly assigned in a 1:1:1 ratio to receive either 500 mg of probenecid, 1000 mg of probenecid, or a matching placebo every 12 h for five days. The patients’ COVID-19 viral load hospitalization, or death from any cause through day 28, as well as safety, were evaluated. COVID-19-related symptoms were assessed at baseline, and on days 3, 5, 10, 15, and 28. The primary endpoints of the study were time to first negative SARS-CoV-2 viral test (or viral clearance) and the proportion of patients that were symptom-free at day 5. A total of 75 patients were randomized, with 25 patients in each group. All of the patients completed the study as planned with no hospitalizations or deaths being reported. The median time to viral clearance was significantly shorter for the probenecid 1000 mg group than for placebo (7 days vs. 11 days, respectively; p < 0.0001), and for the probenecid 500 mg group versus placebo (9 days vs. 11 days, respectively; p < 0.0001). In addition, the median time to viral clearance was significantly shorter for the probenecid 1000 mg group than for the probenecid 500 mg group (7 days vs. 9 days, respectively; p < 0.0001). All patients reported at least one COVID-19-related symptom on days 3 and 5; however, on day 10, a significantly greater proportion of patients receiving probenecid 1000 mg reported the complete resolution of symptoms versus placebo (68% vs. 20%, respectively; p = 0.0006), as well as for those receiving probenecid 500 mg versus placebo (56% vs. 20%, respectively, p = 0.0087). The incidence of adverse events during treatment was similar across all groups for any adverse event, and was 12%. All events were mild with no serious adverse events reported and no discontinuations due to an adverse event. The treatment of patients with symptomatic, mild-to-moderate COVID-19 with probenecid resulted in a significant, dose-dependent decrease in the time to viral clearance and a significantly higher proportion of patients reporting complete symptom resolution by day 10. (Supported by TrippBio; ClinicalTrials.gov number, NCT05442983 and Clinical Trials Registry India number CTRI/2022/07/043726). Full article
(This article belongs to the Special Issue Novel and Repurposed Antiviral Agents)
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12 pages, 23970 KiB  
Communication
Optimization of Anti-SARS-CoV-2 Treatments Based on Curcumin, Used Alone or Employed as a Photosensitizer
by Luisa Zupin, Francesco Fontana, Libera Clemente, Violetta Borelli, Giuseppe Ricci, Maurizio Ruscio and Sergio Crovella
Viruses 2022, 14(10), 2132; https://doi.org/10.3390/v14102132 - 27 Sep 2022
Cited by 7 | Viewed by 1941
Abstract
Curcumin, the bioactive compound of the spice Curcuma longa, has already been reported as a potential COVID-19 adjuvant treatment due to its immunomodulatory and anti-inflammatory properties. In this study, SARS-CoV-2 was challenged with curcumin; moreover, curcumin was also coupled with laser light [...] Read more.
Curcumin, the bioactive compound of the spice Curcuma longa, has already been reported as a potential COVID-19 adjuvant treatment due to its immunomodulatory and anti-inflammatory properties. In this study, SARS-CoV-2 was challenged with curcumin; moreover, curcumin was also coupled with laser light at 445 nm in a photodynamic therapy approach. Curcumin at a concentration of 10 μM, delivered to the virus prior to inoculation on cell culture, inhibited SARS-CoV-2 replication (reduction >99%) in Vero E6 cells, possibly due to disruption of the virion structure, as observed using the RNase protection assay. However, curcumin was not effective as a prophylactic treatment on already-infected Vero E6 cells. Notably, when curcumin was employed as a photosensitizer and blue laser light at 445 nm was delivered to a mix of curcumin/virus prior to the inoculation on the cells, virus inactivation was observed (>99%) using doses of curcumin that were not antiviral by themselves. Photodynamic therapy employing crude curcumin can be suggested as an antiviral option against SARS-CoV-2 infection. Full article
(This article belongs to the Special Issue Novel and Repurposed Antiviral Agents)
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7 pages, 214 KiB  
Opinion
Screening Drugs for Broad-Spectrum, Host-Directed Antiviral Activity: Lessons from the Development of Probenecid for COVID-19
by Ralph A. Tripp and David E. Martin
Viruses 2023, 15(11), 2254; https://doi.org/10.3390/v15112254 - 14 Nov 2023
Cited by 2 | Viewed by 1004
Abstract
In the early stages of drug discovery, researchers develop assays that are compatible with high throughput screening (HTS) and structure activity relationship (SAR) measurements. These assays are designed to evaluate the effectiveness of new and known molecular entities, typically targeting specific features within [...] Read more.
In the early stages of drug discovery, researchers develop assays that are compatible with high throughput screening (HTS) and structure activity relationship (SAR) measurements. These assays are designed to evaluate the effectiveness of new and known molecular entities, typically targeting specific features within the virus. Drugs that inhibit virus replication by inhibiting a host gene or pathway are often missed because the goal is to identify active antiviral agents against known viral targets. Screening efforts should be sufficiently robust to identify all potential targets regardless of the antiviral mechanism to avoid misleading conclusions. Full article
(This article belongs to the Special Issue Novel and Repurposed Antiviral Agents)
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