In Vitro Efficacy of Cyclosporine A and Various Antiseptics and Antiviral Drugs on Adenovirus Genotype 8, a Common Cause of Epidemic Keratoconjunctivitis

Abstract Purpose: To evaluate the in vitro efficacy of cidofovir, ganciclovir, povidone iodine, chlorhexidine, and cyclosporine A on adenovirus genotype 8 Methods: Conjunctival samples were collected from patients with adenoviral conjunctivitis and cultured in A549 cells. Adenovirus diagnosis was confirmed by RT-PCR. For each drug, the 50% cytotoxic concentration (CC₅₀) was determined. Subsequently, the antiviral activity was tested at concentrations below CC₅₀, and the 50% inhibitor concentration (IC₅₀) of drugs was determined.Results: While the IC₅₀ of cidofovir against adenovirus genotype 8 was 3.07 ± 0.8 µM, ganciclovir, povidone iodine, chlorhexidine, and cyclosporine A were not found to be effective against adenovirus genotype 8 at concentrations below the CC₅₀ value.Conclusions: Cidofovir was found effective and the IC₅₀ value was within the ranges in the literature. Ganciclovir and cyclosporine A were found to be ineffective at doses below the cytotoxic dose, povidone iodine and chlorhexidine were found to be highly cytotoxic.

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Disinfectant potential in inactivation of epidemic keratoconjunctivitis-related adenoviruses by potassium peroxymonosulfate

European Journal of Ophthalmology ◽

10.1177/1120672119891408 ◽

2019 ◽

pp. 112067211989140 ◽

Cited By ~ 2

Author(s):

Mei Hashizume ◽

Koki Aoki ◽

Shigeaki Ohno ◽

Nobuyoshi Kitaichi ◽

Nobuyo Yawata ◽

...

Keyword(s):

Polymerase Chain Reaction ◽

Viral Genome ◽

A549 Cells ◽

Human Adenovirus ◽

Polymerase Chain Reaction Analysis ◽

Chain Reaction ◽

Epidemic Keratoconjunctivitis ◽

Polymerase Chain ◽

Potassium Peroxymonosulfate

Purpose: The aim of this study was to test the antiviral effectivity of potassium peroxymonosulfate (RUBYSTA®, KYORIN) against five epidemic keratoconjunctivitis-related types of Human adenovirus D in vitro. Methods: Five types of Human adenovirus D (8, 37, 53, 54 and 56) were incubated with 1% potassium peroxymonosulfate, 0.1% sodium hypochlorite (NaClO) or alcohol-based disinfectant for 30 s or 1 min. These solutions were subjected to measurements of viral titres by infection assays in A549 cells. At day 6 post-infection, both, supernatants and cells, were collected and the viral genome was assessed by real-time polymerase chain reaction analysis. Results: Treatments with 1% potassium peroxymonosulfate led to significant reduction in all tested Human adenovirus D types comparable to disinfecting effects by 0.1% NaClO. Overall, potassium peroxymonosulfate demonstrated sufficient inactivation of the major epidemic keratoconjunctivitis-causing Human adenovirus D to be considered for disinfection and prevention purposes in ophthalmological clinics and hospitals. Conclusion: This study demonstrated that potassium peroxymonosulfate is a promising disinfectant for the prevention of epidemic keratoconjunctivitis nosocomial infections in ophthalmological clinics.

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Potent Antiviral Activity against HSV-1 and SARS-CoV-2 by Antimicrobial Peptoids

Pharmaceuticals ◽

10.3390/ph14040304 ◽

2021 ◽

Vol 14 (4) ◽

pp. 304

Author(s):

Gill Diamond ◽

Natalia Molchanova ◽

Claudine Herlan ◽

John A. Fortkort ◽

Jennifer S. Lin ◽

...

Keyword(s):

Antiviral Activity ◽

Primary Cultures ◽

Antiviral Drugs ◽

Viral Envelope ◽

Distinct Advantage ◽

Head Group ◽

Molecular Features ◽

Viral Envelopes ◽

Hsv 1

Viral infections, such as those caused by Herpes Simplex Virus-1 (HSV-1) and SARS-CoV-2, affect millions of people each year. However, there are few antiviral drugs that can effectively treat these infections. The standard approach in the development of antiviral drugs involves the identification of a unique viral target, followed by the design of an agent that addresses that target. Antimicrobial peptides (AMPs) represent a novel source of potential antiviral drugs. AMPs have been shown to inactivate numerous different enveloped viruses through the disruption of their viral envelopes. However, the clinical development of AMPs as antimicrobial therapeutics has been hampered by a number of factors, especially their enzymatically labile structure as peptides. We have examined the antiviral potential of peptoid mimics of AMPs (sequence-specific N-substituted glycine oligomers). These peptoids have the distinct advantage of being insensitive to proteases, and also exhibit increased bioavailability and stability. Our results demonstrate that several peptoids exhibit potent in vitro antiviral activity against both HSV-1 and SARS-CoV-2 when incubated prior to infection. In other words, they have a direct effect on the viral structure, which appears to render the viral particles non-infective. Visualization by cryo-EM shows viral envelope disruption similar to what has been observed with AMP activity against other viruses. Furthermore, we observed no cytotoxicity against primary cultures of oral epithelial cells. These results suggest a common or biomimetic mechanism, possibly due to the differences between the phospholipid head group makeup of viral envelopes and host cell membranes, thus underscoring the potential of this class of molecules as safe and effective broad-spectrum antiviral agents. We discuss how and why differing molecular features between 10 peptoid candidates may affect both antiviral activity and selectivity.

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Antiviral Effects of Plant Extracts Used in the Treatment of Important Animal Viral Diseases

World s Veterinary Journal ◽

10.54203/scil.2021.wvj67 ◽

2021 ◽

Vol 11 (4) ◽

pp. 521-533

Author(s):

Gamil Sayed Gamil Zeedan ◽

Abeer Mostafa Abdalhamed

Keyword(s):

Antiviral Activity ◽

Viral Infection ◽

Plant Extracts ◽

Rna Viruses ◽

Biological Activities ◽

Antiviral Drugs ◽

Antiviral Compounds ◽

Antiviral Activities

The goal of this review was to highlight some plant species that have significant antiviral activity against DNA and RNA viruses in vitro and in vivo although more research is needed to address safety issues, drug interactions, and the possibility of using them in combination with other natural products. Viral infection plays an important role in human and animal diseases. Although there have been advances in immunization and antiviral drugs, there is still a lack of protective vaccines and effective antiviral drugs in human and veterinary medicine. The lack of effective antivirals necessitates the search for new effective antiviral compounds. Plants are naturally gifted at synthesizing antiviral compounds. They are rich sources of phytochemicals with different biological activities, including antiviral activities as a result of advanced analytical chemistry, standard virus assays, and development of standardization and extraction methods. Plant extracts have a wide variety of active compounds, including flavonoids, terpenoids, lignans, sulphides, polyphenolics, coumarins, saponins, furyl compounds, alkaloids, polyines, thiophenes, proteins, and peptides. Moreover, certain volatile oils have indicated a high level of antiviral activity. Replication, assembly, and release, as well as targeting virus host-specific interactions capable of inhibiting several viruses, could help the development of broad-spectrum antivirals for the prevention and control of viral pathogens. The in vitro antiviral activities of Erythroxylum deciduum, Lacistema hasslerianum (chodat), Xylopia aromatica, Heteropteris aphrodisiaca, Acacia nilotica (gum arabic tree), Lippia graveolens (Guettarda angelica (Velvetseed), Prunus myrtifolia, and Symphyopappus plant extracts can inhibite viral replication, and interfer with the early stages of viral adsorption of DNA viruses. However, Boesenbergia rotunda plant extracts have inhibited RNA viruses. A potent anti-SARS-CoV-2 inhibitor with B. rotunda extract and panduratin A after viral infection drastically suppresses SARS-CoV-2 infectivity in Vero E6 cells.

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The citrus flavonoid naringenin impairs the in vitro infection of human cells by Zika virus

Scientific Reports ◽

10.1038/s41598-019-52626-3 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 11

Author(s):

Allan Henrique Depieri Cataneo ◽

Diogo Kuczera ◽

Andrea Cristine Koishi ◽

Camila Zanluca ◽

Guilherme Ferreira Silveira ◽

...

Keyword(s):

Antiviral Activity ◽

Zika Virus ◽

Fruits And Vegetables ◽

Antiviral Treatment ◽

Clinical Manifestations ◽

A549 Cells ◽

Human Monocyte ◽

Zikv Infection ◽

Independent Manner

Abstract The Zika virus (ZIKV) is an arthropod-borne virus that belongs to the Flaviviridae family. The ZIKV infection is usually asymptomatic or is associated with mild clinical manifestations; however, increased numbers of cases of microcephaly and birth defects have been recently reported. To date, neither a vaccine nor an antiviral treatment has become available to control ZIKV replication. Among the natural compounds recognized for their medical properties, flavonoids, which can be found in fruits and vegetables, have been found to possess biological activity against a variety of viruses. Here, we demonstrate that the citrus flavanone naringenin (NAR) prevented ZIKV infection in human A549 cells in a concentration-dependent and ZIKV-lineage independent manner. NAR antiviral activity was also observed when primary human monocyte-derived dendritic cells were infected by ZIKV. NAR displayed its antiviral activity when the cells were treated after infection, suggesting that NAR acts on the viral replication or assembly of viral particles. Moreover, a molecular docking analysis suggests a potential interaction between NAR and the protease domain of the NS2B-NS3 protein of ZIKV which could explain the anti-ZIKV activity of NAR. Finally, the results support the potential of NAR as a suitable candidate molecule for developing anti-ZIKV treatments.

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Potent Antiviral Activity Against HSV-1 and SARS-CoV-2 by Antimicrobial Peptoids

10.20944/preprints202103.0258.v1 ◽

2021 ◽

Author(s):

Gill Diamond ◽

Natalia Molchanova ◽

Claudine Herlan ◽

John A. Fortkort ◽

Jennifer S. Lin ◽

...

Keyword(s):

Antiviral Activity ◽

Viral Infections ◽

Primary Cultures ◽

Antiviral Drugs ◽

Viral Envelope ◽

Distinct Advantage ◽

Head Group ◽

Viral Envelopes ◽

Hsv 1

Viral infections, such as those caused by Herpes Simplex Virus-1 (HSV-1) and SARS-CoV-2, affect millions of people each year. However, there are few antiviral drugs that can effectively treat these infections. The standard approach in the development of antiviral drugs involves the identification of a unique viral target, followed by the design of an agent that addresses that target. Antimicrobial peptides (AMPs) represent a novel source of potential antiviral drugs. AMPs have been shown to inactivate numerous different enveloped viruses through the disruption of their viral envelopes. However, the clinical development of AMPs as antimicrobial therapeutics has been hampered by a number of factors, especially their structure as peptides. We have examined the antiviral potential of peptoid mimics of AMPs (sequence-specific N-substituted glycine oligomers). These peptoids have the distinct advantage of being insensitive to proteases, and also exhibit increased bioavailability and stability. Our results demonstrate that several peptoids exhibit potent in vitro antiviral activity against both HSV-1 and SARS-CoV-2 when incubated prior to infection. Visualization by cryo-EM shows viral envelope disruption similar to what has been observed with AMP activity against other viruses. This suggests a common or biomimetic mechanism, possibly due to the differences between the phospholipid head group makeup of viral envelopes and host cell membranes. Furthermore, we observed no cytotoxicity against primary cultures of oral epithelial cells, thus underscoring the potential of this class of molecules as safe and effective broad-spectrum antiviral agents.

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Vδ2 T-Cells Kill ZIKV-Infected Cells by NKG2D-Mediated Cytotoxicity

Microorganisms ◽

10.3390/microorganisms7090350 ◽

2019 ◽

Vol 7 (9) ◽

pp. 350 ◽

Cited By ~ 1

Author(s):

Cimini ◽

Sacchi ◽

De Minicis ◽

Bordoni ◽

Casetti ◽

...

Keyword(s):

Immune Response ◽

T Cells ◽

Antiviral Activity ◽

A549 Cells ◽

Protective Immune Response ◽

Zikv Infection ◽

Protein Levels ◽

Infected Cells

An expansion of effector/activated Vδ2 T-cells was recently described in acute Zika virus (ZIKV)-infected patients, but their role in the protective immune response was not clarified. The aim of this study was to define the antiviral activity of Vδ2 T-cells against ZIKV-infected cells. The Vδ2 T-cells expansion and their cytotoxic activity against ZIKV-infected cells were tested in vitro and analyzed by RT-PCR and flow cytometry. We found that ZIKV infection was able to induce Vδ2 T-cells expansion and sensitized A549 cells to Vδ2-mediated killing. Indeed, expanded Vδ2 T-cells killed ZIKV-infected cells through degranulation and perforin release. Moreover, ZIKV infection was able to increase the expression on A549 cells of NKG2D ligands (NKG2DLs), namely MICA, MICB, and ULBP2, at both the mRNA and protein levels, suggesting the possible involvement of these molecules in the recognition by NKG2D-expressing Vδ2 T-cells. Indeed, the killing of ZIKV-infected cells by expanded Vδ2 T-cells was mediated by NKG2D/NKG2DL interaction as NKG2D neutralization abrogated Vδ2 cytotoxicity. Our data showed a strong antiviral activity of Vδ2 T-cells against ZIKV-infected cells, suggesting their involvement in the protective immune response. Other studies are necessary to investigate whether the lack of Vδ2 T-cells expansion in vivo may be associated with disease complications.

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In Vitro Effectiveness of Povidone-Iodine onAcanthamoeba Isolates from Human Cornea

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.42.9.2232 ◽

1998 ◽

Vol 42 (9) ◽

pp. 2232-2234 ◽

Cited By ~ 26

Author(s):

Simonetta Gatti ◽

Claudia Cevini ◽

Antonella Bruno ◽

Gabriella Penso ◽

Paolo Rama ◽

...

Keyword(s):

Antiviral Activity ◽

Contact Lens ◽

Povidone Iodine ◽

Ocular Infection ◽

Human Cornea

ABSTRACT Acanthamoeba keratitis is a severe ocular infection secondary to accidental macro- or microscopic trauma of the cornea. Starting in 1985, a dramatic increase of this infection was recorded along with the spread of contact lens use. This protozoal disease is difficult to treat because of the scarcity of efficacious topical and systemic drugs. We evaluated the in vitro effectiveness of povidone-iodine (PVP-I [Betadine]), an agent with broad antibacterial and antiviral activity, compared to that of chlorhexidine (CXD), a cationic antiseptic, on Acanthamoeba isolates from patients with amebic keratitis. The results showed that PVP-I solution from 0.5 to 2.5% has a better antiamebic activity both on trophic and cystic stages of Acanthamoeba spp. than does CXD.

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In Vitro Evaluation of the Antiviral Activity of Methylene Blue Alone or in Combination against SARS-CoV-2

Journal of Clinical Medicine ◽

10.3390/jcm10143007 ◽

2021 ◽

Vol 10 (14) ◽

pp. 3007

Author(s):

Mathieu Gendrot ◽

Priscilla Jardot ◽

Océane Delandre ◽

Manon Boxberger ◽

Julien Andreani ◽

...

Keyword(s):

Methylene Blue ◽

Antiviral Activity ◽

Viral Entry ◽

Low Cost ◽

Antiviral Drug ◽

Effective Concentration ◽

Rt Pcr ◽

Post Entry ◽

Median Effective Concentration

A new severe acute respiratory syndrome coronavirus (SARS-CoV-2) causing coronavirus diseases 2019 (COVID-19), which emerged in Wuhan, China in December 2019, has spread worldwide. Currently, very few treatments are officially recommended against SARS-CoV-2. Identifying effective, low-cost antiviral drugs with limited side effects that are affordable immediately is urgently needed. Methylene blue, a synthesized thiazine dye, may be a potential antiviral drug. Antiviral activity of methylene blue used alone or in combination with several antimalarial drugs or remdesivir was assessed against infected Vero E6 cells infected with two clinically isolated SARS-CoV-2 strains (IHUMI-3 and IHUMI-6). Effects both on viral entry in the cell and on post-entry were also investigated. After 48 h post-infection, the viral replication was estimated by RT-PCR. The median effective concentration (EC50) and 90% effective concentration (EC90) of methylene blue against IHUMI-3 were 0.41 ± 0.34 µM and 1.85 ± 1.41 µM, respectively; 1.06 ± 0.46 µM and 5.68 ± 1.83 µM against IHUMI-6. Methylene blue interacted at both entry and post-entry stages of SARS-CoV-2 infection in Vero E6 cells as retrieved for hydroxychloroquine. The effects of methylene blue were additive with those of quinine, mefloquine and pyronaridine. The combinations of methylene blue with chloroquine, hydroxychloroquine, desethylamodiaquine, piperaquine, lumefantrine, ferroquine, dihydroartemisinin and remdesivir were antagonist. These results support the potential interest of methylene blue to treat COVID-19.

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Antiviral Activity of 3D, a Butene Lactone Derivative Against Influenza A Virus In Vitro and In Vivo

Viruses ◽

10.3390/v13020278 ◽

2021 ◽

Vol 13 (2) ◽

pp. 278

Author(s):

Zhenya Wang ◽

Jieyu Fang ◽

Jiao Luo ◽

Duoduo Hou ◽

Yayun Tan ◽

...

Keyword(s):

Antiviral Activity ◽

Influenza A Virus ◽

Influenza A ◽

Early Stage ◽

A549 Cells ◽

Respiratory Pathogen ◽

Apoptosis Pathway ◽

Mitochondrial Apoptosis Pathway

Influenza A virus is a highly variable and contagious respiratory pathogen that can cause annual epidemics and it poses an enormous threat to public health. Therefore, there is an urgent need for a new generation of antiviral drugs to combat the emergence of drug-resistant strains of the influenza virus. A novel series of butene lactone derivatives were screened and the compound 3D was selected, as it exhibited in vitro potential antiviral activity against A/Weiss/43 H1N1 virus with low toxicity. In addition, 3D dose-dependently inhibited the viral replication, expression of viral mRNA and viral proteins. 3D exerted a suppressive effect on A/Virginia/ATCC2/2009 H1N1 and A/California/2/2014 H3N2 in vitro. The time-of-addition analysis indicated that 3D suppressed H1N1 in the early stage of its life cycle. A/Weiss/43 H1N1-induced apoptosis in A549 cells was reduced by 3D via the mitochondrial apoptosis pathway. 3D could decrease the production of H1N1-induced pro-inflammatory cytokines that are induced by H1N1 in vitro and in vivo. The administration of 3D reduced lung lesions and virus load in vivo. These results suggest that 3D, which is a butene lactone derivative, is a promising agent for the treatment of influenza A virus infection.

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Antiviral activity of 5-aminolevulinic acid against variants of severe acute respiratory syndrome coronavirus 2

Tropical Medicine and Health ◽

10.1186/s41182-021-00397-x ◽

2022 ◽

Vol 50 (1) ◽

Author(s):

Mya Myat Ngwe Tun ◽

Takaya Sakura ◽

Yasuteru Sakurai ◽

Yohei Kurosaki ◽

Daniel Ken Inaoka ◽

...

Keyword(s):

Severe Acute Respiratory Syndrome ◽

Antiviral Activity ◽

Aminolevulinic Acid ◽

Antiviral Drug ◽

Antiviral Effect ◽

Drug Candidate ◽

Rt Pcr ◽

Ferrous Citrate ◽

Virus Inhibition

Abstract Background Genetic variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) began to emerge in 2020 and have been spreading globally during the coronavirus disease 2019 (COVID-19) pandemic. Despite the presence of different COVID-19 vaccines, the discovery of effective antiviral therapeutics for the treatment of patients infected with SARS-CoV-2 are still urgently needed. A natural amino acid, 5-aminolevulinic acid (5-ALA), has exhibited both antiviral and anti-inflammatory activities. In a previous study, we demonstrated an in vitro antiviral effect of 5-ALA against SARS-CoV-2 infection without significant cytotoxicity. In the present study, we sought to investigate whether 5-ALA with or without sodium ferrous citrate (SFC) can inhibit in vitro both the original SARS-CoV-2 Wuhan strain and its variants, including the Alpha, Beta, Gamma and Delta strains. Methods The antiviral activity of ALA with or without SFC was determined in Vero-E6 cell. The virus inhibition was quantified by real time RT-PCR. Results Co-administration of 5-ALA and SFC inhibited the Wuhan, Alpha and Delta variants of SARS-CoV-2 with IC50 values of 235, 173 and 397 µM, respectively, and the Beta and Gamma variants with IC50 values of 1311 and 1516 µM. Conclusion Our study suggests that 5-ALA with SFC warrants accelerated clinical evaluation as an antiviral drug candidate for treating patients infected with SARS-CoV-2 variants.

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