scholarly journals Antiviral Activity of Broad-Spectrum and Enterovirus-Specific Inhibitors against Clinical Isolates of Enterovirus D68

2015 ◽  
Vol 59 (12) ◽  
pp. 7782-7785 ◽  
Author(s):  
Liang Sun ◽  
Adam Meijer ◽  
Mathy Froeyen ◽  
Linlin Zhang ◽  
Hendrik Jan Thibaut ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Protease Inhibitors ◽  
Broad Spectrum ◽  
Mechanisms Of Action ◽  
Structural Explanation ◽  
Weak Inhibitor ◽  
3C Protease ◽  
Enterovirus D68 ◽  
Inhibitor Resistance ◽  
Specific Inhibitors

ABSTRACTWe investigated the susceptibility of 10 enterovirus D68 (EV-D68) isolates (belonging to clusters A, B, and C) to (entero)virus inhibitors with different mechanisms of action. The 3C-protease inhibitors proved to be more efficient than enviroxime and pleconaril, which in turn were more effective than vapendavir and pirodavir. Favipiravir proved to be a weak inhibitor. Resistance to pleconaril maps to V69A in the VP1 protein, and resistance to rupintrivir maps to V104I in the 3C protease. A structural explanation of why both substitutions may cause resistance is provided.

Role of GS-5734 (Remdesivir) in inhibiting SARS-CoV and MERS-CoV: The expected role of GS-5734 (Remdesivir) in COVID-19 (2019-nCoV) - VYTR hypothesis.

2020 ◽  
Vol 11 (SPL1) ◽  
Author(s):  
Vityala Yethindra
Keyword(s):  
Clinical Trials ◽  
Antiviral Activity ◽  
Protease Inhibitors ◽  
Human Body ◽  
Broad Spectrum ◽  
Rna Synthesis ◽  
Rna Viruses ◽  
Improved Outcomes ◽  
The Family

Coronaviruses (CoVs) are enveloped RNA viruses related to the family Coronaviridae, the order Nirdovales, and observed in humans and other mammals. In December 2019, many pneumonia cases reported by patients with unknown causes, mainly associated with seafood and wet animal market in Wuhan, China, and where clinically resembled viral pneumonia. At present, there is no existence of antiviral drugs for the treatment of CoV infections. The results of our study are GS-5734 strongly inhibits SARS-CoV and MERS-CoV in HAE cells, GS-5734 inhibits CoVs at early stages in replication by inhibiting viral RNA synthesis, the absence of ExoN-mediated proofreading in viruses sensitive to treatment with GS-5734. Protease inhibitors can show improved outcomes in some coronaviruses, but mostly 99% of protease inhibitors bind to proteins present in the human body, and only 1% attacks on existed viruses. The expected role of GS-5734 (Remdesivir) in the 2019-nCoV - VYTR hypothesis explained. As broad-spectrum drugs are capable of inhibiting CoV infections, GS-5734 is a broad-spectrum drug and may show inhibition on CoV infections and 2019-nCoV. GS-5734 will show desired results regarding antiviral activity against 2019-nCoV as it showed potent antiviral activity in other CoVs. More clinical trials and experiments needed to prove that GS-5734 (Remdesivir) is a potential and effective drug to treat 2019-nCoV.

scholarly journals Conservation of Amino Acids in Human Rhinovirus 3C Protease Correlates with Broad-Spectrum Antiviral Activity of Rupintrivir, a Novel Human Rhinovirus 3C Protease Inhibitor

2005 ◽  
Vol 49 (2) ◽  
pp. 619-626 ◽  
Author(s):  
S. L. Binford ◽  
F. Maldonado ◽  
M. A. Brothers ◽  
P. T. Weady ◽  
L. S. Zalman ◽  
...  
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Antiviral Activity ◽  
Broad Spectrum ◽  
Amino Acid Sequences ◽  
Human Rhinovirus ◽  
Clinical Isolates ◽  
Sequence Analyses ◽  
3C Protease

ABSTRACT The picornavirus 3C protease is required for the majority of proteolytic cleavages that occur during the viral life cycle. Comparisons of published amino acid sequences from 6 human rhinoviruses (HRV) and 20 human enteroviruses (HEV) show considerable variability in the 3C protease-coding region but strict conservation of the catalytic triad residues. Rupintrivir (formerly AG7088) is an irreversible inhibitor of HRV 3C protease with potent in vitro activity against all HRV serotypes (48 of 48), HEV strains (4 of 4), and untyped HRV field isolates (46 of 46) tested. To better understand the relationship between in vitro antiviral activity and 3C protease-rupintrivir binding interactions, we performed nucleotide sequence analyses on an additional 21 HRV serotypes and 11 HRV clinical isolates. Antiviral activity was also determined for 23 HRV clinical isolates and four additional HEV strains. Sequence comparison of 3C proteases (n = 58) show that 13 and 11 of the 14 amino acids that are involved in side chain interactions with rupintrivir are strictly conserved among HRV and HEV, respectively. These sequence analyses are consistent with the comparable in vitro antiviral potencies of rupintrivir against all HRV serotypes, HRV isolates, and HEV strains tested (50% effective concentration range, 3 to 183 nM; n = 125). In summary, the conservation of critical amino acid residues in 3C protease and the observation of potent, broad-spectrum antipicornavirus activity of rupintrivir highlight the advantages of 3C protease as an antiviral target.

A novel tricationic fullerene C60 as broad-spectrum antimicrobial photosensitizer: mechanisms of action and potentiation with potassium iodide

2021 ◽  
Vol 20 (3) ◽  
pp. 327-341
Author(s):  
Maximiliano L. Agazzi ◽  
Javier E. Durantini ◽  
Ezequiel D. Quiroga ◽  
M. Gabriela Alvarez ◽  
Edgardo N. Durantini
Keyword(s):  
Potassium Iodide ◽  
Broad Spectrum ◽  
Mechanisms Of Action ◽  
Fullerene C60

scholarly journals Broad-Spectrum Antiviral Strategies and Nucleoside Analogues

Viruses ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 667
Author(s):  
Robert J. Geraghty ◽  
Matthew T. Aliota ◽  
Laurent F. Bonnac
Keyword(s):  
Public Health ◽  
Severe Acute Respiratory Syndrome ◽  
Broad Spectrum ◽  
Vaccine Development ◽  
Fast Response ◽  
Mechanisms Of Action ◽  
Public Health Emergency ◽  
Nucleoside Analogues ◽  
The Family ◽  
Antiviral Nucleoside

The emergence or re-emergence of viruses with epidemic and/or pandemic potential, such as Ebola, Zika, Middle East Respiratory Syndrome (MERS-CoV), Severe Acute Respiratory Syndrome Coronavirus 1 and 2 (SARS and SARS-CoV-2) viruses, or new strains of influenza represents significant human health threats due to the absence of available treatments. Vaccines represent a key answer to control these viruses. However, in the case of a public health emergency, vaccine development, safety, and partial efficacy concerns may hinder their prompt deployment. Thus, developing broad-spectrum antiviral molecules for a fast response is essential to face an outbreak crisis as well as for bioweapon countermeasures. So far, broad-spectrum antivirals include two main categories: the family of drugs targeting the host-cell machinery essential for virus infection and replication, and the family of drugs directly targeting viruses. Among the molecules directly targeting viruses, nucleoside analogues form an essential class of broad-spectrum antiviral drugs. In this review, we will discuss the interest for broad-spectrum antiviral strategies and their limitations, with an emphasis on virus-targeted, broad-spectrum, antiviral nucleoside analogues and their mechanisms of action.

scholarly journals Broad-Spectrum Antiviral Activity of 3D8, a Nucleic Acid-Hydrolyzing Single-Chain Variable Fragment (scFv), Targeting SARS-CoV-2 and Multiple Coronaviruses In Vitro

Viruses ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 650
Author(s):  
Gunsup Lee ◽  
Shailesh Budhathoki ◽  
Geum-Young Lee ◽  
Kwang-ji Oh ◽  
Yeon Kyoung Ham ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Antiviral Activity ◽  
Broad Spectrum ◽  
Recombinant Antibody ◽  
Therapeutic Effects ◽  
Single Chain Variable Fragment ◽  
Single Chain ◽  
Diarrhea Virus ◽  
3D8 Scfv

The virus behind the current pandemic, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the etiology of novel coronavirus disease (COVID-19) and poses a critical public health threat worldwide. Effective therapeutics and vaccines against multiple coronaviruses remain unavailable. Single-chain variable fragment (scFv), a recombinant antibody, exhibits broad-spectrum antiviral activity against DNA and RNA viruses owing to its nucleic acid-hydrolyzing property. The antiviral activity of 3D8 scFv against SARS-CoV-2 and other coronaviruses was evaluated in Vero E6 cell cultures. Viral growth was quantified with quantitative RT-qPCR and plaque assay. The nucleic acid-hydrolyzing activity of 3D8 was assessed through abzyme assays of in vitro viral transcripts and cell viability was determined by MTT assay. We found that 3D8 inhibited the replication of SARS-CoV-2, human coronavirus OC43 (HCoV-OC43), and porcine epidemic diarrhea virus (PEDV). Our results revealed the prophylactic and therapeutic effects of 3D8 scFv against SARS-CoV-2 in Vero E6 cells. Immunoblot and plaque assays showed the reduction of coronavirus nucleoproteins and infectious particles, respectively, in 3D8 scFv-treated cells. These data demonstrate the broad-spectrum antiviral activity of 3D8 against SARS-CoV-2 and other coronaviruses. Thus, it could be considered a potential antiviral countermeasure against SARS-CoV-2 and zoonotic coronaviruses.

scholarly journals The effectiveness of antiviral agents with broad-spectrum activity against chikungunya virus varies between host cell lines

2018 ◽  
Vol 26 ◽  
pp. 204020661880758 ◽  
Author(s):  
Evelyn J Franco ◽  
Jaime L Rodriquez ◽  
Justin J Pomeroy ◽  
Kaley C Hanrahan ◽  
Ashley N Brown
Keyword(s):  
Antiviral Activity ◽  
Host Cell ◽  
Cell Line ◽  
Cell Lines ◽  
Broad Spectrum ◽  
Chikungunya Virus ◽  
Plaque Assay ◽  
A549 Cells ◽  
Western Hemisphere ◽  
Viral Burden

Chikungunya virus (CHIKV) is a mosquito-borne virus that has recently emerged in the Western Hemisphere. Approved antiviral therapies or vaccines for the treatment or prevention of CHIKV infections are not available. This study aims to evaluate the antiviral activity of commercially available broad-spectrum antivirals against CHIKV. Due to host cell-specific variability in uptake and intracellular processing of drug, we evaluated the antiviral effects of each agent in three cell lines. Antiviral activities of ribavirin (RBV), interferon-alfa (IFN-α) and favipiravir (FAV) were assessed in CHIKV-infected Vero, HUH-7, and A549 cells. CHIKV-infected cells were treated with increasing concentrations of each agent for three days and viral burden was quantified by plaque assay on Vero cells. Cytotoxic effects of RBV, FAV and IFN-α were also evaluated. Antiviral activity differed depending on the cell line used for evaluation. RBV had the greatest antiviral effect in HUH-7 cells (EC50 = 2.575 µg/mL); IFN-α was most effective in A549 cells (EC50 = 4.235 IU/mL); and FAV in HUH-7 cells (EC50 = 20.00 μg/mL). The results of our study show FAV and IFN-α are the most promising candidates, as their use led to substantial reductions in viral burden at clinically achievable concentrations in two human-derived cell lines. FAV is an especially attractive candidate for further investigation due to its oral bioavailability. These findings also highlight the importance of cell line selection for preclinical drug trials.

Pyrrolinone-Based HIV Protease Inhibitors. Design, Synthesis, and Antiviral Activity: Evidence for Improved Transport

1995 ◽  
Vol 117 (45) ◽  
pp. 11113-11123 ◽  
Author(s):  
Amos B Smith ◽  
Ralph Hirschmann ◽  
Alexander Pasternak ◽  
Mark C. Guzman ◽  
Akihisa Yokoyama ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Protease Inhibitors ◽  
Hiv Protease ◽  
Hiv Protease Inhibitors ◽  
Design Synthesis
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