Flaviviruses such as Dengue, West Nile, and Zika viruses are mosquito-borne RNA viruses that can cause serious diseases in humans. To develop effective drugs for treating these viruses’ infections, we create a new approach for developing common or shared drugs that may work for several different viral species of flaviviruses. It is based on the conserved RNA-dependent RNA polymerase (RdRp), which is the key enzyme for viral replication. We built up a common structure of RdRps (POLcon) from their consensus sequence. A conserved Triple-D structural motif was identified at the active site of POLcon that has been used for virtual compound screening. We have identified three inhibitors that have potent activities against Dengue, West Nile, and Zika viruses. All these three inhibitors are Benzothiophene derivatives. This is the first report of Benzothiophene-derived compounds as inhibitors for flaviviruses. Furthermore, our approach has provided a proof-of-concept that it is feasible to identify shared drugs for several different viral species of flaviviruses.

Algal lectin Griffithsin (GRFT) is a well-known mannose-binding protein which has broad-spectrum antiviral activity against several important infectious viruses including HIV, HCV, and SARS-CoV-2. Therefore, GRFT has been brought great attention to antiviral therapeutic development. In this report, we have tested GRFT’s activity against the lethal Ebola virus in vitro and in vivo. Our data have shown that the IC₅₀ value is about 42 nM for inhibiting Zaire Ebola virus (EBOV) infection in vitro. The preliminary in vivo mice model using mouse-adapted EBOV has also shown a certain efficacy for delayed mortality compared to the control animals. A GRFT pull-down experiment using viral particles demonstrates that GRFT can bind to N-glycans of EBOV. Thus, it can be concluded that GRFT, through binding to viral glycans, may block Ebola virus infection and has potential for the treatment of Ebola virus disease (EVD).

Flaviviruses such as Dengue, West Nile, and Zika viruses are mosquito-borne RNA viruses that can cause serious diseases in humans. To develop effective drugs for treating these viruses’ infections, we create a new approach for developing common or shared drugs that may work for several different viral species of flaviviruses. It is based on the conserved RNA-dependent RNA polymerase (RdRp), which is the key enzyme for viral replication. We built up a common structure of RdRps (POLcon) from their consensus sequence. A conserved Triple-D structural motif was identified at the active site of POLcon that has been used for virtual compound screening. We have identified three inhibitors that have potent activities against Dengue, West Nile, and Zika viruses. All these three inhibitors are Benzothiophene derivatives. This is the first report of Benzothiophene-derived compounds as broad-spectrum inhibitors for flaviviruses. Furthermore, our approach has provided a proof-of-concept that it is feasible to identify shared drugs for several different viral species of flaviviruses.

Algal lectin Griffithsin (GRFT) is a well-known mannose-binding protein which has a broad-spectrum antiviral activity against several important infectious viruses including HIV, HCV, and SARS-CoV-2. Therefore, GRFT has been brought great attention to antiviral therapeutic development. In this report, we have tested GRFT’s activity against the lethal Ebola virus in vitro and in vivo. Our data has shown that the IC50 value is about 42 nM for inhibiting Zair Ebola virus (EBOV) infection in vitro. The preliminary in vivo mice model using mouse-adapted EBOV has also shown a certain efficacy for delayed mortality compared to the control animals. GRFT pulldown experiment by viral particles demonstrates that GRFT can bind to N-glycans of EBOV. Thus, it can be concluded that GRFT through binding to the viral glycans for blocking Ebola virus infection and has potential for treating Ebola virus disease (EVD).