A biaryl sulfonamide derivative as a novel inhibitor of filovirus infection.

A biaryl sulfonamide derivative as a novel inhibitor of filovirus infection. Antiviral Res. 2020 Sep 15;:104932 Authors: Isono M, Furuyama W, Kuroda M, Kondoh T, Igarashi M, Kajihara M, Yoshida R, Manzoor R, Okuya K, Miyamoto H, Feldmann H, Marzi A, Sakaitani M, Nanbo A, Takada A Abstract Ebolaviruses and marburgviruses, members of the family Filoviridae, are known to cause fatal diseases often associated with hemorrhagic fever. Recent outbreaks of Ebola virus disease in West African countries and the Democratic Republic of the Congo have made clear the urgent need for the development of therapeutics and vaccines against filoviruses. Using replication-incompetent vesicular stomatitis virus (VSV) pseudotyped with the Ebola virus (EBOV) envelope glycoprotein (GP), we screened a chemical compound library to obtain new drug candidates that inhibit filoviral entry into target cells. We descovered a biaryl sulfonamide derivative that suppressed in vitro infection mediated by GPs derived from all known human-pathogenic filoviruses. To determine the inhibitory mechanism of the compound, we monitored each entry step (attachment, internalization, and membrane fusion) using lipophilic tracer-labelled ebolavirus-like particles and found that the compound efficiently blocked fusion between the viral envelope and the endosomal membrane during cellular entry. However, the compound did not block the interaction of GP with the Niemann-Pick C1 protein...
Source: Antiviral Research - Category: Virology Authors: Tags: Antiviral Res Source Type: research