Classic and new strategies to fight arboviruses: effect of antiviral drugs and skin bacteria on virus infectivity

The past decades the world has experienced a large increase in outbreaks of mosquito-borne viruses, such as chikungunya virus (CHIKV) of the Alphavirus genus and Zika virus (ZIKV) of the Flavivirus genus. Due to increased travelling, climate change and adaptation of the mosquito vectors to urbanization, their geographic distribution has expanded and is still augmenting worldwide. Despite the important global health threat, there are currently no good antiviral therapies available to prevent or treat alphavirus- and flavivirus-induced disease. A classic strategy to fight viruses is the use of antiviral drugs to treat viral disease in infected humans. We evaluated the activity of a panel of compounds against the neglected and emerging Mayaro virus (MAYV). We first set up and optimized a cell-based antiviral assay that could be used for high-throughput screening in the future. We then identified that the repurposed drugs favipiravir, suramin and EIDD-1931 inhibited MAYV replication in vitro and we characterized their mechanisms of action against MAYV. In addition to the classic strategy of antiviral drugs, it would be necessary to develop novel strategies to prevent infections of mosquito-borne viruses. It has been shown that manipulation of the mosquito microbiome is a promising strategy to prevent virus transmission from the mosquito to the human host. Moreover, it has been shown for other viruses (respiratory and enteric viruses) that host microbiota can affect viral infectivity. Since the first site of alpha- and flavivirus inoculation is the biting site in the skin, we studied possible interactions between bacteria that colonize the skin and alpha- and flaviviruses. We first determined the effect of skin bacteria and bacterial cell wall components on alphavirus and flavivirus infectivity in vitro. Virus infectivity was reduced due to a direct interaction between bacterial cell wall components and viral particles. We further characterized the role of skin bacteria, using a ZIKV mouse infection model. Prior to ZIKV infection, mice were treated with an antibiotic cream at the inoculation site to locally deplete the skin bacteria. Topical antibiotic treatment significantly decreased the median survival of ZIKV-infected mice and increased viral loads in the draining lymph node and the serum at early stages of infection. Both the in vitro and in vivo data thus suggest that (skin) bacteria might have a protective effect against arboviruses, making it worthwile to further investigate the potential of bacteria or probiotics in the fight against arboviruses.

Jaar van publicatie:2022

Toegankelijkheid:Embargoed