Crystallographic and Pharmacological Studies of Antiviral Agents Against Human Rhinovirus

1990 ◽  
pp. 9-28
Author(s):  
Thomas J. Smith ◽  
John Badger ◽  
Marcia Kremer ◽  
Marcos Oliveira ◽  
Michael G. Rossmann ◽  
...  
Keyword(s):  
Antiviral Agents ◽  
Human Rhinovirus ◽  
Pharmacological Studies

The Site of Attachment in Human Rhinovirus 14 for Antiviral Agents That Inhibit Uncoating

2014 ◽  
pp. 198-205
Author(s):  
Thomas J. Smith ◽  
Marcia J. Kremer ◽  
Ming Luo ◽  
Gerrit Vriend ◽  
Edward Arnold ◽  
...  
Keyword(s):  
Antiviral Agents ◽  
Human Rhinovirus

scholarly journals Multiple Classes of Antiviral Agents ExhibitIn VitroActivity against Human Rhinovirus Type C

2013 ◽  
Vol 58 (3) ◽  
pp. 1546-1555 ◽  
Author(s):  
Chris Mello ◽  
Esmeralda Aguayo ◽  
Madeleine Rodriguez ◽  
Gary Lee ◽  
Robert Jordan ◽  
...  
Keyword(s):  
Kinase Inhibitor ◽  
Antiviral Agents ◽  
Airway Epithelial Cells ◽  
Human Rhinovirus ◽  
Dependent Manner ◽  
Airway Epithelial ◽  
Content Type ◽  
Type C ◽  
Rna Replicon

ABSTRACTHuman rhinovirus type C (HRV-C) is a newly discovered enterovirus species frequently associated with exacerbation of asthma and other acute respiratory conditions. Until recently, HRV-C could not be propagatedin vitro, hampering in-depth characterization of the virus replication cycle and preventing efficient testing of antiviral agents. Herein we describe several subgenomic RNA replicon systems and a cell culture infectious model for HRV-C that can be used for antiviral screening. The replicon constructs consist of genome sequences from HRVc15, HRVc11, HRVc24, and HRVc25 strains, with the P1 capsid region replaced by aRenillaluciferase coding sequence. Following transfection of the replicon RNA into HeLa cells, the constructs produced time-dependent increases in luciferase signal that can be inhibited in a dose-dependent manner by known inhibitors of HRV replication, including the 3C protease inhibitor rupintrivir, the nucleoside analog inhibitor MK-0608, and the phosphatidylinositol 4-kinase IIIβ (PI4K-IIIβ) kinase inhibitor PIK93. Furthermore, with the exception of pleconaril and pirodavir, the other tested classes of HRV inhibitors blocked the replication of full-length HRVc15 and HRVc11 in human airway epithelial cells (HAEs) that were differentiated in the air-liquid interface, exhibiting antiviral activities similar to those observed with HRV-16. In summary, this study is the first comprehensive profiling of multiple classes of antivirals against HRV-C, and the set of newly developed quantitative HRV-C antiviral assays represent indispensable tools for the identification and evaluation of novel panserotype HRV inhibitors.

scholarly journals Structural analysis of a series of antiviral agents complexed with human rhinovirus 14.

1988 ◽  
Vol 85 (10) ◽  
pp. 3304-3308 ◽  
Author(s):  
J. Badger ◽  
I. Minor ◽  
M. J. Kremer ◽  
M. A. Oliveira ◽  
T. J. Smith ◽  
...  
Keyword(s):  
Structural Analysis ◽  
Antiviral Agents ◽  
Human Rhinovirus

The site of attachment in human rhinovirus 14 for antiviral agents that inhibit uncoating

Science ◽  
1986 ◽  
Vol 233 (4770) ◽  
pp. 1286-1293 ◽  
Author(s):  
T. Smith ◽  
M. Kremer ◽  
M Luo ◽  
G Vriend ◽  
E Arnold ◽  
...  
Keyword(s):  
Antiviral Agents ◽  
Human Rhinovirus

scholarly journals Specificity of human rhinovirus 2Apro is determined by combined spatial properties of four cleavage site residues

2013 ◽  
Vol 94 (7) ◽  
pp. 1535-1546 ◽  
Author(s):  
David Neubauer ◽  
Martina Aumayr ◽  
Irene Gösler ◽  
Tim Skern
Keyword(s):  
Amino Acids ◽  
Substrate Specificity ◽  
Cleavage Site ◽  
Antiviral Agents ◽  
Genetic Group ◽  
Human Rhinovirus ◽  
C Terminus ◽  
Group B

The 2A proteinase (2Apro) of human rhinoviruses cleaves the virally encoded polyprotein between the C terminus of VP1 and its own N terminus. Poor understanding of the 2Apro substrate specificity of this enzyme has hampered progress in developing inhibitors that may serve as antiviral agents. We show here that the 2Apro of human rhinovirus (HRV) 1A and 2 (rhinoviruses from genetic group A) cannot self-process at the HRV14 (a genetic group B rhinovirus) cleavage site. When the amino acids in the cleavage site of HRV2 2Apro (Ile-Ile-Thr-Thr-Ala*Gly-Pro-Ser-Asp) were singly or doubly replaced with the corresponding HRV14 residues (Asp-Ile-Lys-Ser-Tyr*Gly-Leu-Gly-Pro) at positions from P3 to P2′, HRV1A and HRV2 2Apro cleavage took place at WT levels. However, when three or more positions of the HRV1A or 2 2Apro were substituted (e.g. at P2, P1 and P2′), cleavage in vitro was essentially eliminated. Introduction of the full HRV14 cleavage site into a full-length clone of the HRV1A and transfection of HeLa cells with a transcribed RNA did not give rise to viable virus. In contrast, revertant viruses bearing cysteine at the P1 position or proline at P2′ were obtained when an RNA bearing the three inhibitory amino acids was transfected. Reversions in the enzyme affecting substrate specificity were not found in any of the in vivo experiments. Modelling of oligopeptide substrates onto the structure of HRV2 2Apro revealed no appreciable differences in residues of HRV2 and HRV14 in the respective substrate binding sites, suggesting that the overall shape of the substrate is important in determining binding efficiency.

scholarly journals An Evaluation of Traditional Persian Medicine for the Management of SARS-CoV-2

2020 ◽  
Vol 11 ◽  
Author(s):  
Roodabeh Bahramsoltani ◽  
Roja Rahimi
Keyword(s):  
Medicinal Plants ◽  
Clinical Studies ◽  
Antiviral Agents ◽  
Molecular Structures ◽  
Antiviral Compounds ◽  
Pharmacological Studies ◽  
Persian Medicine ◽  
Life Threatening ◽  
Traditional Persian Medicine ◽  
Therapeutic Activities

A new coronavirus causing severe acute respiratory syndrome (SARS-CoV-2) has emerged and with it, a global investigation of new antiviral treatments and supportive care for organ failure due to this life-threatening viral infection. Traditional Persian Medicine (TPM) is one of the most ancient medical doctrines mostly known with the manuscripts of Avicenna and Rhazes. In this paper, we first introduce a series of medicinal plants that would potentially be beneficial in treating SARS-CoV-2 infection according to TPM textbooks. Then, we review medicinal plants based on the pharmacological studies obtained from electronic databases and discuss their mechanism of action in SARS-CoV-2 infection. There are several medicinal plants in TPM with cardiotonic, kidney tonic, and pulmonary tonic activities, protecting the lung, heart, and kidney, the three main vulnerable organs in SARS-CoV-2 infection. Some medicinal plants can prevent “humor infection”, a situation described in TPM which has similar features to SARS-CoV-2 infection. Pharmacological evaluations are in line with the therapeutic activities of several plants mentioned in TPM, mostly through antiviral, cytoprotective, anti-inflammatory, antioxidant, and anti-apoptotic mechanisms. Amongst the primarily-introduced medicinal plants from TPM, rhubarb, licorice, garlic, saffron, galangal, and clove are the most studied plants and represent candidates for clinical studies. The antiviral compounds isolated from these plants provide novel molecular structures to design new semisynthetic antiviral agents. Future clinical studies in healthy volunteers as well as patients suffering from pulmonary infections are necessary to confirm the safety and efficacy of these plants as complementary and integrative interventions in SARS-CoV-2 infection.

Phytochemical and pharmacological studies of Crotalaria madurensis leaves

Planta Medica ◽  
2008 ◽  
Vol 74 (09) ◽  
Author(s):  
SHM Hala ◽  
SAM Mohamed ◽  
TI Magada ◽  
SA El Batran ◽  
DE Omayma
Keyword(s):  
Pharmacological Studies
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