Targeting ER Import And Activation Of Viral Glycoproteins: Towards Broad-Spectrum Antivirals

The VIGILANT consortium is dedicated to tackling the global threat posed by emerging viruses, exemplified by the COVID-19 pandemic and the Ebola epidemic in Western Africa. These events have emphasized the profound impact of such viruses on human health and economic stability. Moreover, anthropogenic factors, notably climate change, will result in an increase in the frequency of outbreaks caused by these viruses in the future. To address this vulnerability, the VIGILANT consortium pursues the development of antivirals with broad-spectrum activity. Pioneering research conducted by the consortium has identified the inhibition of the Sec61 channel and virus-activating host proteases as a promising strategy. The consortium's efforts are centered on addressing priority diseases defined by the World Health Organization due to their epidemic potential and the lack of countermeasures. Thus, the VIGILANT consortium aims to provide new insights into the protease dependence of emerging viruses, including Ebola virus, Marburg virus, Nipah virus, Zika virus, and Chikungunya virus. Furthermore, VIGILANT will develop inhibitors of the virus-activating proteases furin and cathepsin B/L that are safe and exert broad and potent antiviral activity in cell culture and animal models and are thus ready for clinical evaluation. Furthermore, VIGILANT will devise inhibitors targeting Sec61 and will determine breadth of antiviral activity and potential resistance mechanisms. To achieve these ambitious goals, VIGILANT has assembled an array of partners with unique resources and expertise. These partners have demonstrated success in inhibitor development, protease profiling, protein structure determination, and analysis of antivirals. By leveraging their collective capabilities, the VIGILANT consortium aims to provide important insights into ER import and activation of viral glycoproteins and to bring about a quantum leap in pandemic preparedness - the development of broad-spectrum antiviral