Abstract
Coxsackievirus B3 (CVB3) is the most common cause of acute and chronic viral myocarditis, primarily in children, while human adenovirus infections represent a significant cause of morbidity and mortality worldwide, in people of all ages. A series of novel 2-benzoxyl-phenylpyridine derivatives were evaluated for their potential antiviral activities against CVB3 and adenovirus type 7 (ADV7). Preliminary assays indicated that some of these compounds exhibited excellent antiviral effects on both CVB3 and ADV7 viruses; they could effectively inhibit virus-induced cytopathic effects, reduce viral progeny yields, and had similar or superior antiviral activities compared with the control drug, ribavirin. Further, these compounds targeted the early stages of CVB3 replication in cells, including viral RNA replication and protein synthesis, rather than inactivating the virus directly, inhibiting virus adsorption/entry, or affecting viral release from cells. Our data demonstrate that the tested 2-benzoxyl-phenylpyridine derivatives are effective inhibitors of CVB3 and ADV7, raising the possibility that these compounds might be feasible candidates for anti-viral agents.
Highlights
Diseases caused by viral infection are a major public health issue
A series of 2-benzoxyl-phenylpyridine derivatives were tested against Coxsackievirus B3 (CVB3) and adenovirus type 7 (ADV7) in cell-based assays
Since CVB3 and ADV7 infections cause marked cytopathic effects (CPEs), we evaluated the antiviral properties of these compounds by analysis of CPEs in Hep-2 and human cervical carcinoma cells (HeLa) cells infected with
Summary
Diseases caused by viral infection are a major public health issue. Coxsackievirus B3 (CVB3)is non-enveloped, single-stranded (+) RNA virus, belonging to the picornavirus family. CVB3 is considered a pathogen of significant importance, as it is the most common cause of acute and chronic viral myocarditis, primarily in children [1]. CVB3 is associated with the development of respiratory infections, aseptic meningitis, encephalitis, pancreatitis, hepatitis, and acute episodes of hand, foot, and mouth disease [2,3,4,5]. There is no specific drug approved for the treatment of CVB3 infection [6]. Some reports have presented effective candidates for treatment of CVB3 [7,8], and many molecules that block CVB replication in vitro, attacking different points of the viral life-cycle, have been reported in the past few decades; none have received final market approval because of adverse side effects or unsatisfactory antiviral activity [9,10]. It is of great interest to search for novel and effective antiviral drug candidates against CVB3
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