Development and Effects of Influenza Antiviral Drugs

Abstract

Influenza virus is a highly contagious zoonotic respiratory disease that causes seasonal outbreaks each year and unpredictable pandemics occasionally with high morbidity and mortality rates, posing a great threat to public health worldwide. Besides the limited effect of vaccines, the problem is exacerbated by the lack of drugs with strong antiviral activity against all flu strains. Currently, there are two classes of antiviral drugs available that are chemosynthetic and approved against influenza A virus for prophylactic and therapeutic treatment, but the appearance of drug-resistant virus strains is a serious issue that strikes at the core of influenza control. There is therefore an urgent need to develop new antiviral drugs. Many reports have shown that the development of novel bioactive plant extracts and microbial extracts has significant advantages in influenza treatment. This paper comprehensively reviews the development and effects of chemosynthetic drugs, plant extracts, and microbial extracts with influenza antiviral activity, hoping to provide some references for novel antiviral drug design and promising alternative candidates for further anti-influenza drug development.

Keywords: chemosynthetic drugs; drug resistance; influenza virus; microbial metabolites; plant extracts.

Figure 1

Replication cycle of influenza virus and targets of anti-influenza drugs. (a) Influenza virus hemagglutinin (HA) binds to sialylated host cell receptors, and then is internalised into endosomes through multiple endocytosis pathways. (b) Acidification of the endosome leads to activation of the M2 proton channel and virion acidification, resulting in virus uncoating and the release of viral genome into the cytoplasm, where it is further transported to the nucleus to begin genome replication. (c) In the nucleus, influenza virus begins to synthesize viral mRNAs. (d) HA, neuraminidase (NA) and M2 are processed in the Golgi body and the endoplasmic reticulum, and then transported to the cell surface. (e) Influenza virus polymerase can synthesize both viral mRNAs and vRNAs. vRNAs are first converted into positive-stranded cRNAs, and then new vRNAs can be synthesized using cRNAs as templates. (f) Viral proteins and genomic RNA are transported to the cell surface to assemble progeny viruses. Then, influenza virus neuraminidase (NA) cuts off the HA-receptor bond to allow progeny viruses to be released from the surface of the infected cell and proceed to infect new cells. The sites of action of antiviral drugs are shown in red.

Figure 2

The molecular structures of chemical synthesis drugs.