Arbidol: The current demand, strategies, and antiviral mechanisms

Abstract

BackgroundHigh morbidity and mortality of influenza virus infection have made it become one of the most lethal diseases threatening public health; the lack of drugs with strong antiviral activity against virus strains exacerbates the problem.MethodsTwo independent researchers searched relevant studies using Embase, PubMed, Web of Science, Google Scholar, and MEDLINE databases from its inception to December 2022.ResultsBased on the different antiviral mechanisms, current antiviral strategies can be mainly classified into virus‐targeting approaches such as neuraminidase inhibitors, matrix protein 2 ion channel inhibitors, polymerase acidic protein inhibitors and other host‐targeting antivirals. However, highly viral gene mutation has underscored the necessity of novel antiviral drug development. Arbidol (ARB) is a Russian‐made indole‐derivative small molecule licensed in Russia and China for the prevention and treatment of influenza and other respiratory viral infections. ARB also has inhibitory effects on many other viruses such as severe acute respiratory syndrome coronavirus 2, Coxsackie virus, respiratory syncytial virus, Hantaan virus, herpes simplex virus, and hepatitis B and C viruses. ARB is a promising drug which can not only exert activity against virus at different steps of virus replication cycle, but also directly target on hosts before infection to prevent virus invasion.ConclusionARB is a broad‐spectrum antiviral drug that inhibits several viruses in vivo and in vitro, with high safety profile and low resistance; the antiviral mechanisms of ARB deserve to be further explored and more high‐quality clinical studies are required to establish the efficacy and safety of ARB.

Indole-containing pharmaceuticals: targets, pharmacological activities, and SAR studies

“…[94][95][96] It is a hydrophobic molecule capable of forming aromatic stacking interactions with certain amino acid residues, which contributes to its ability to directly act against viruses. Its antiviral activity may also be due to its interactions with the aromatic residues within the viral glycoproteins involved in fusion and cellular recognition, 97,98 the plasma membrane to interfere with clathrin-mediated exocytosis and intracellular trafficking, 99 or directly with the viral lipid envelope itself. As indicated by its SAR graph, the binding pocket of the HA protomers with arbidol is a hydrophobic cavity at the interface of the HA protomers in the upper region of the stem.…”

Host factors of SARS-CoV-2 in infection, pathogenesis, and long-term effects

“…Some compounds exert antiviral effects by acting on host receptors. Arbidol (ARB), as a broad-spectrum antiviral, can interfere with virus entry or the membrane fusion of SARS-CoV-2 ( Kang et al., 2023 ). On the one hand, ARB inhibits the interaction between the S protein and ACE2.…”

Inhibitors of the Structural and Nonstructural Proteins of Alphaviruses

“…54,55 Arbidol is an anti-influenza medication and has been shown to have antiviral effects on other viruses as well as immunomodulatory effects. 56 ■ STRUCTURAL PROTEINS OF ALPHAVIRUSES AS TARGETS A few studies have reported small molecule inhibitors of CP, E2, and 6K proteins. The multifunctional capsid protein is essential in genome encapsulation, virus budding, and virion assembly.…”

“…This effort also led to the identification of resistant clones that bear G117R or D119 K mutation close to the binding pocket of nsP3MD. While there is no direct evidence yet that the compounds interfere with the biochemical roles of the nsP3MD, the significant loss of Additionally, a couple of in silico studies have predicted that naringenin (56), a lanthionine synthetase C-like 2 ligand, NSC61610 (57), and macrodomain 1 inhibitor (NSC670283, 58) have high affinity for CHIKV's nsP3MD. 118,119 Nonstructural Protein 4.…”

“…Nevertheless, in vivo evaluation of chloroquine as a therapeutic agent revealed that it exacerbates acute Chikungunya disease in macaques and offers no clinical benefits as an antiviral when administered to humans infected with CHIKV. , Chloroquine has also been shown to enhance the replication of SFV and encephalomyocarditis virus in mice . Another drug that is known to block the attachment or entry of CHIKV to Vero (EC 50 value of 12.2 μM) and MRC5 (EC 50 value of 11.7 μM) cells is the antiviral Arbidol ( 6 , umifenovir). , Arbidol is an anti-influenza medication and has been shown to have antiviral effects on other viruses as well as immunomodulatory effects …”