A fight against viral infections: host factors and antiviral therapies against positive-strand RNA viruses

Viral outbreaks can have devastating impacts on both human health and society. To develop effective antiviral treatments, it is important to understand the interactions between the host and the virus at the molecular level. In the first part of the thesis, we investigated the relationship between mosquito-borne viruses like chikungunya virus (CHIKV), dengue (DENV), Zika virus (ZIKV) and West Nile virus (WNV), and autophagy, a cellular degradative pathway. We discovered that the role of autophagy and autophagy-related proteins (ATG) can vary depending on the virus. For example, depletion of BNIP3 showed a marked increase in CHIKV replication, suggesting that BNIP3 is a new host factor that inhibits CHIKV early in its replication cycle. Moreover, knockout of ATG7 and ATG16L1 reduced DENV-2 viral particle production, suggesting the pro-viral role of these proteins in post-replicative stages of DENV-2 replication cycle.In the second part of this thesis, we examined the effectiveness of some antiviral agents against SARS-CoV-2. We found that boceprevir can inhibit β-coronaviruses by binding to the SARS-CoV-2 3CLpro protease's catalytic pocket. Resveratrol and pterostilbene also showed promise in inhibiting SARS-CoV-2 production by acting on post-entry stages of the replication cycle. Overall, this thesis provides new insights into the molecular mechanisms of mosquito-borne viruses and highlights potential avenues for developing antiviral therapies against SARS-CoV-2