Arbidol as a broad-spectrum antiviral: an update

Abstract

Arbidol (ARB) is a Russian-made small indole-derivative molecule, licensed in Russia and China for prophylaxis and treatment of influenza and other respiratory viral infections. It also demonstrates inhibitory activity against other viruses, enveloped or not, responsible for emerging or globally prevalent infectious diseases such as hepatitis B and C, gastroenteritis, hemorrhagic fevers or encephalitis. In this review, we will explore the possibility and pertinence of ARB as a broad-spectrum antiviral, after a careful examination of its physico-chemical properties, pharmacokinetics, toxicity, and molecular mechanisms of action. Recent studies suggest that ARB's dual interactions with membranes and aromatic amino acids in proteins may be central to its broad-spectrum antiviral activity. This could impact on the virus itself, and/or on cellular functions or critical steps in virus-cell interactions, thereby positioning ARB as both a direct-acting antiviral (DAA) and a host-targeting agent (HTA). In the context of recent studies in animals and humans, we will discuss the prospective clinical use of ARB in various viral infections.

Keywords: Antiviral therapy; Arbidol; Entry; Fusion; Hepatitis C virus; Influenza.

Fig. 1

Chemical structures of arbidol (A), sulfonyl-arbidol (B), and sulfinyl-arbidol (C). In D, structure of a prototypic aryl-thio-indole molecule, as synthesized by La Regina et al. (2013).

Fig. 2

Broad-spectrum activity of ARB and its molecular mechanisms of action at the cellular level. The different steps of the viral life cycle inhibited by ARB are indicated in blue boxes. Potential effect of ARB on other viruses or families of viruses are mentioned in orange. Blue arrows and text indicate the consequences of ARB on cellular pathways and virions. For clarity and regarding current knowledge about the molecular mechanisms of ARB, we only show the clathrin-dependent endocytosis pathway. MW, membranous web, ER, endoplasmic reticulum.