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

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.

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

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.

scholarly journals Antiviral Activity of the G-Quadruplex Ligand TMPyP4 against Herpes Simplex Virus-1

Viruses ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 196
Author(s):  
Sara Artusi ◽  
Emanuela Ruggiero ◽  
Matteo Nadai ◽  
Beatrice Tosoni ◽  
Rosalba Perrone ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Dna Replication ◽  
Herpes Simplex ◽  
Antiviral Activity ◽  
Herpes Simplex Virus 1 ◽  
Tem Analysis ◽  
Infected Cells ◽  
Simplex Virus ◽  
Hsv 1

The herpes simplex virus 1 (HSV-1) genome is extremely rich in guanine tracts that fold into G-quadruplexes (G4s), nucleic acid secondary structures implicated in key biological functions. Viral G4s were visualized in HSV-1 infected cells, with massive virus cycle-dependent G4-formation peaking during viral DNA replication. Small molecules that specifically interact with G4s have been shown to inhibit HSV-1 DNA replication. We here investigated the antiviral activity of TMPyP4, a porphyrin known to interact with G4s. The analogue TMPyP2, with lower G4 affinity, was used as control. We showed by biophysical analysis that TMPyP4 interacts with HSV-1 G4s, and inhibits polymerase progression in vitro; in infected cells, it displayed good antiviral activity which, however, was independent of inhibition of virus DNA replication or entry. At low TMPyP4 concentration, the virus released by the cells was almost null, while inside the cell virus amounts were at control levels. TEM analysis showed that virus particles were trapped inside cytoplasmatic vesicles, which could not be ascribed to autophagy, as proven by RT-qPCR, western blot, and immunofluorescence analysis. Our data indicate a unique mechanism of action of TMPyP4 against HSV-1, and suggest the unprecedented involvement of currently unknown G4s in viral or antiviral cellular defense pathways.

scholarly journals Entry of Herpes Simplex Virus Type 1 into Primary Sensory Neurons In Vitro Is Mediated by Nectin-1/HveC

2003 ◽  
Vol 77 (5) ◽  
pp. 3307-3311 ◽  
Author(s):  
Sarah M. Richart ◽  
Scott A. Simpson ◽  
Claude Krummenacher ◽  
J. Charles Whitbeck ◽  
Lewis I. Pizer ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Sensory Neurons ◽  
Virus Type ◽  
Herpes Simplex Virus Type ◽  
Primary Cultures ◽  
Simplex Virus ◽  
Hsv 1

ABSTRACT Primary cultures of rat and mouse sensory neurons were used to study the entry of herpes simplex virus type 1 (HSV-1). Soluble, truncated nectin-1 but not HveA prevented viral entry. Antibodies against nectin-1 also blocked infection of rat neurons. These results indicate that nectin-1 is the primary receptor for HSV-1 infection of sensory neurons.

Antiviral activity of 1,4-disubstituted-1,2,3-triazoles against HSV-1 in vitro

2021 ◽  
Author(s):  
Daiane J Viegas ◽  
Verônica D da Silva ◽  
Camilla D Buarque ◽  
David C Bloom ◽  
Paula A Abreu
Keyword(s):  
Antiviral Activity ◽  
Hsv 1

Antiherpesvirus Activity of the Combination of 5-iodo-2′-deoxycytidine with methotrexate: An in vitro and in vivo Study

1994 ◽  
Vol 5 (5) ◽  
pp. 283-289
Author(s):  
C. Cremonesi ◽  
C. Scarpini ◽  
R. Bianchi ◽  
A. Radaelli ◽  
M. Gimelli ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Dihydrofolate Reductase ◽  
Reductase Inhibitor ◽  
Cellular Viability ◽  
Cutaneous Lesions ◽  
Guinea Pig Model ◽  
Simplex Virus ◽  
Hsv 1

We evaluated the in vitro and in vivo antiviral activity of the deoxyribonucleoside analogue 5-iodo-2′-deoxycytidine (IDC) combined with the dihydrofolate reductase inhibitor methotrexate (MTX) on herpes simplex virus types 1 and 2 (HSV-1, HSV-2). The IDC-MTX combination synergistically inhibited HSV-1 and HSV-2 replication in vitro at concentrations that did not reduce cellular viability and was very effective in reducing the severity of cutaneous lesions in the experimental guinea pig model in vivo. The antiviral activity of the IDC-MTX combination in guinea pigs was also compared with that of acyclovir and was demonstrated to be higher.

scholarly journals Tryptophan Trimers and Tetramers Inhibit Dengue and Zika Virus Replication by Interfering with Viral Attachment Processes

2020 ◽  
Vol 64 (3) ◽  
Author(s):  
Antonios Fikatas ◽  
Peter Vervaeke ◽  
Belén Martínez-Gualda ◽  
Olaia Martí-Marí ◽  
Sam Noppen ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Zika Virus ◽  
Antiviral Agent ◽  
Viral Envelope ◽  
Pharmacokinetic Studies ◽  
Host Cell Membrane ◽  
Viral Attachment ◽  
Virus Attachment ◽  
Domain Iii

ABSTRACT Here, we report a class of tryptophan trimers and tetramers that inhibit (at low micromolar range) dengue and Zika virus infection in vitro. These compounds (AL family) have three or four peripheral tryptophan moieties directly linked to a central scaffold through their amino groups; thus, their carboxylic acid groups are free and exposed to the periphery. Structure-activity relationship (SAR) studies demonstrated that the presence of extra phenyl rings with substituents other than COOH at the N1 or C2 position of the indole side chain is a requisite for the antiviral activity against both viruses. The molecules showed potent antiviral activity, with low cytotoxicity, when evaluated on different cell lines. Moreover, they were active against laboratory and clinical strains of all four serotypes of dengue virus as well as a selected group of Zika virus strains. Additional mechanistic studies performed with the two most potent compounds (AL439 and AL440) demonstrated an interaction with the viral envelope glycoprotein (domain III) of dengue 2 virus, preventing virus attachment to the host cell membrane. Since no antiviral agent is approved at the moment against these two flaviviruses, further pharmacokinetic studies with these molecules are needed for their development as future therapeutic/prophylactic drugs.

scholarly journals Ultrastructure of the Effects of Pyrrolidine-fused Chlorins on the Replication of HSV-1

2008 ◽  
Vol 14 (S3) ◽  
pp. 137-138
Author(s):  
António P.A. Matos ◽  
Ana R.N. Santos ◽  
Maria F. Caeiro ◽  
Maria A.F. Faustino ◽  
M.G.P.M.S. Neves ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Antiviral Drugs ◽  
Cell Complex ◽  
New Drugs ◽  
Viral Resistance ◽  
Porphyrin Derivatives ◽  
Cellular Target ◽  
Immunocompromised Hosts ◽  
Hsv 1

Currently, only few antiviral drugs of proven effectiveness exist against virus of the Herpesviridae family and viral resistance to these drugs, especially in the immunocompromised hosts, has encouraged research for new drugs. Some porphyrin derivatives revealed a significant antiviral activity against HSV-1 virus. However the cellular target of the porphyrin derivatives in the virus-cell complex remains unknown.

Lipid prodrugs of phosphonoacids: greatly enhanced antiviral activity of 1-O-octadecyl-sn-glycero-3-phosphonoformate in HIV-1, HSV-1 and HCMV-infected cells, in vitro

1996 ◽  
Vol 31 (1-2) ◽  
pp. 59-67 ◽  
Author(s):  
Karl Y. Hostetler ◽  
Ganesh D. Kini ◽  
James R. Beadle ◽  
Kathy A. Aldern ◽  
Michael F. Gardner ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Infected Cells ◽  
Hiv 1 ◽  
Hsv 1

Polysulfonates Derived from Metal Thiolate Complexes as Inhibitors of HIV-1 and Various other Enveloped Viruses In Vitro

2002 ◽  
Vol 13 (3) ◽  
pp. 185-195 ◽  
Author(s):  
Donald E Bergstrom ◽  
Xiaoping Lin ◽  
Troy D Wood ◽  
Myriam Witvrouw ◽  
Satoru Ikeda ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Palladium Complex ◽  
Platinum Complex ◽  
Cadmium Complex ◽  
Junin Virus ◽  
Tacaribe Virus ◽  
Junín Virus ◽  
Hiv 1 ◽  
Hsv 1

Sodium 2-mercaptoethanesulfonate reacts with the metal ions Pd(II), Pt(II), Ag(I), Cd(II) and Zn(II) to yield complexes containing multiple anionic sulfonate sites. On the basis of spectroscopic and other analytical data the complexes were assigned the tentative molecular formulas: Pd6(SCH2CH2SO3Na)12, Ptn(SCH2CH2SO3Na)2n+2, Agn(SCH2CH2SO3Na)n, Na2Zn4(SCH2CH2SO3Na)10, and Na2Cd4(SCH2CH2SO3Na)10. The complexes displayed a variety of differences in activity towards DNA and RNA viruses. The platinum complex showed no measurable cytotoxicity and exhibited a spectrum of antiviral activity resembling that of dextran sulfate. It was active against HIV-1 and HIV-2, herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2), thymidine kinase-deficient HSV-1, human cytomegalovirus, vesicular stomatitis virus (VSV), influenza A virus, respiratory syncytial virus (RSV), Sindbis virus, Junin virus and Tacaribe virus. The palladium complex also showed no measurable cytotoxicity, but was completely inactive against most viruses, with one notable exception: both HIV-1 and HIV-2 were substantially inhibited by the palladium complex. The silver complex showed significantly less antiviral activity and greater cytotoxicity than the platinum complex but did show some selectivity against RSV. The zinc complex showed only modest activity against VSV, RSV, Junin virus, and Tacaribe virus, and like the silver compound was more cytotoxic than either the platinum or palladium complex. The cadmium complex was toxic to all of the cell lines used for in vitro evaluation of antiviral activity. Based on these results, the platinum and palladium compounds appear to be promising candidates for further studies, that is, as vaginal microbicides in the prevention of genital HIV and/or HSV transmission.

scholarly journals BX795-Organic Acid Coevaporates: Evaluation of Solid-State Characteristics, In Vitro Cytocompatibility and In Vitro Activity against HSV-1 and HSV-2

Pharmaceutics ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 1920
Author(s):  
Yogesh Sutar ◽  
Tejabhiram Yadavalli ◽  
Sagar Kumar Paul ◽  
Sudipta Mallick ◽  
Raghuram Koganti ◽  
...  
Keyword(s):  
Citric Acid ◽  
Antiviral Activity ◽  
Organic Acids ◽  
Organic Acid ◽  
Tartaric Acid ◽  
Fumaric Acid ◽  
Amorphous Systems ◽  
Amorphous System ◽  
Hsv 1

BX795 is a TANK binding kinase-1 inhibitor that has shown excellent therapeutic activity in murine models of genital and ocular herpes infections on topical delivery. Currently, only the BX795 free base and its hydrochloride salt are available commercially. Here, we evaluate the ability of various organic acids suitable for vaginal and/or ocular delivery to form BX795 salts/cocrystals/co-amorphous systems with the aim of facilitating pharmaceutical development of BX795. We characterized BX795-organic acid coevaporates using powder X-ray diffractometry, Fourier-transform infrared spectroscopy (FT-IR), Raman spectroscopy, 1H-nuclear magnetic resonance spectroscopy, thermogravimetric analysis (TGA), and differential scanning calorimetry (DSC) to elucidate the interaction between BX795 and various organic acids such as taurine, maleic acid, fumaric acid, tartaric acid, and citric acid. Furthermore, using human corneal epithelial cells and HeLa cells, we evaluated BX795-organic acid coevaporates for in vitro cytocompatibility and in vitro antiviral activity against herpes simplex virus-type 1 (HSV-1) and type-2 (HSV-2). Our studies indicate that BX795 forms co-amorphous systems with tartaric acid and citric acid. Interestingly, the association of organic acids with BX795 improved its thermal stability. Our in vitro cytocompatibility and in vitro antiviral studies to screen suitable BX795-organic acid coevaporates for further development show that all BX795-organic acid systems, at a concentration equivalent to 10 µM BX795, retained antiviral activity against HSV-1 and HSV-2 but showed differential cytocompatibility. Further, dose-dependent in vitro cytocompatibility and antiviral activity studies on the BX795-fumaric acid system, BX795-tartaric acid co-amorphous system, and BX795-citric acid co-amorphous system show similar antiviral activity against HSV-1 and HSV-2 compared to BX795, whereas only the BX795-citric acid co-amorphous system showed higher in vitro cytocompatibility compared to BX795.

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