In vitro characterisation of a pleconaril/pirodavir-like compound with potent activity against rhinoviruses

Abstract BACKGROUND: Rhinovirus infections do not only cause common colds, but may also trigger severe exacerbations of asthma and chronic obstructive pulmonary disease (COPD). Even though rhinoviruses have been the focus of extensive drug development efforts in the past, an anti-rhinoviral drug still has to make it to the market. In the past, the viral capsid protein VP1 has been shown to be an important target for the development of antiviral molecules. Furthermore, many different chemical scaffolds appear to possess the properties that are required to inhibit virus replication by this mechanism of action. I-6602, an analogue of the rhinovirus inhibitor pirodavir, was previously identified as a potent inhibitor of rhinovirus infection. Here, we describe the antiviral activity of its analogue ca603, a molecule with a modified linker structure, and corroborate its mechanism of action as a capsid binder. FINDINGS: The molecule ca603 shows antiviral activity against a panel of rhino-and enteroviruses. Cross-resistance is observed against viruses with mutations that render them resistant to the inhibitory effect of the capsid binder pleconaril and thermostability assays demonstrate that the compound binds and stabilizes the viral capsid. Binding of the molecule to the VP1 protein is corroborated by in silico modeling. CONCLUSIONS: It is confirmed that ca603 inhibits rhinovirus replication by interaction with the VP1 protein and, by this, allows to further expand the chemical diversity of capsid-binding molecules

The role of human herpesvirus 8 in diabetes mellitus type 2: State of the art and a medical hypothesis

Diabetes is a common chronic disease due to an altered glucose metabolism, caused by the quantitative and/or qualitative dysfunction of the insulin hormone. Two types of diabetes are recognized: juvenile diabetes, or type 1, which has an autoimmune origin, and adult diabetes, or type 2 (DMT2), which covers 90-95 % of all diabetic patients.The causes of DMT2 are not yet clear: heredity, life style, nutrition, and environment are considered the main risk factors. Several viral infections, namely cytomegalovirus, coxsackie and other enteroviruses, rubella and hepatitis C virus, have been claimed to be associated with some forms of diabetes. The direct role of viruses as a cause or as a risk of type 1 diabetes has been amply described in several recent reviews. Therefore, this review focuses attention on the role of a human herpes pathogenic virus in the onset of DMT2. By carrying out an analysis of recent literature, we describe the findings reported on an extremely deceitful virus, such as Human Herpes virus 8, and present a medical hypothesis on a possible relationship between this virus and DMT2