Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA. Electronic address:
Published: December 2018
AI Article Synopsis
Article Abstract
The aquaculture industry is growing rapidly to meet the needs for global protein consumption. Viral diseases in aquaculture are quite challenging due to lack of treatment options as well as limited injection-delivery vaccines, which are costly. Thus, water-immersion antiviral treatments are highly desirable. This study focused on broad-spectrum, light-activated antivirals that target the viral membrane (envelope) of viruses to prevent viral-cell membrane fusion, ultimately blocking viral entry into cells. Of the tested small-molecules, JL122, a new broad-spectrum antiviral previously unexplored against aquatic viruses, blocked infection of three aquatic rhabdoviruses (IHNV, VHSV and SVCV) in cell culture and in two live fish challenge models. Importantly, JL122 inhibited transmission of IHNV from infected to uninfected rainbow trout. Further, the effective antiviral concentrations were not toxic to cells or susceptible fish. These results show promise for JL122 to become an immersion treatment option for outbreaks of aquatic enveloped viral infections.
Chumakov Federal Scientific Center for Research and Development of Immune-and-Biological Products of Russian Academy of Sciences (Institute of Poliomyelitis), Moscow, Russia; Institute of Translational Medicine and Biotechnology, Sechenov First Moscow State Medical University, Moscow, Russia.
The orthoflavivirus NS1 protein is a relatively understudied target for the design of broad-spectrum anti-orthoflaviviral drugs. Currently, the NS1 protein structures of tick-borne orthoflaviviruses have not been published yet, but these structures can be modelled by homology, thus generating a large amount of structural data. We performed homology modelling of the NS1 protein structures of epidemiologically significant orthoflaviviruses and analysed the possibility of using these models in ensemble docking-based virtual screening.
The recent surge in emerging viral infections warrants the design of broad-spectrum antivirals. We aim to develop a lead molecule that targets a common biochemical feature of many enveloped viruses, membrane fusion. To achieve the broad-spectrum ability, instead of targeting the fusion machinery, we plan to modulate the physicochemical properties of the host and viral membranes to block fusion.
Enterovirus (EV) is a genus that includes a large diversity of viruses spread around the world. They are the main cause of numerous diseases with seasonal clusters, like hand-foot-mouth disease (HFMD). A vaccine is marketed in China for the prevention of HFMD caused by EV-A71.
The Ras GTPase-activating protein SH3-domain-binding protein 1 (G3BP1) serves as a formidable barrier to viral replication by generating stress granules (SGs) in response to viral infections. Interestingly, viruses, including SARS-CoV-2, have evolved defensive mechanisms to hijack SG proteins like G3BP1 for the dissipation of SGs that lead to the evasion of the host's immune responses. Previous research has demonstrated that the interaction between the NTF2-like domain of G3BP1 (G3BP1) and the intrinsically disordered N-terminal domain (NTD-N) of the N-protein plays a crucial role in regulating viral replication and pathogenicity.
Enterovirus-D68 (EV-D68) was first identified in 1962 in pediatric patients with acute respiratory conditions in California, USA (US). From the 1970s to 2005, EV-D68 was underestimated due to limited data and serotyping methods. In 2014, the United States experienced outbreaks of acute flaccid myelitis (AFM) in children EV-D68 positive.
