**9. Future perspectives**

**3.** Development of a universal vaccine that protects against influenza regardless of what influenza viruses are circulating. These includes vaccine targeting the HA stalk domain

In addition to antiviral drugs and vaccines, several novel therapeutic alternatives may prove to be beneficial in the near future. The long-acting inhaled neuraminidase inhibitor CS-8958 (also known as R-118958) has shown promising results in murine models of influenza treatment while a polymerase inhibitor, T-705 (Toyama Chemical), that inhibits viral RNA polymerase has been found to be effective against all three influenza virus types (A, B and C) and to some extent against other RNA viruses, including hemorrhagic fever viruses. The drug, DAS181, a fusion construct that includes the sialidase from *Actinomyces viscosus*, affects the viral attachment process during the early stages of influenza replication. Another study demonstrated the antiviral properties of chlorogenic acid (CHA) and its inhibitory effect on A/PuertoRico/8/1934 (H1N1) and oseltamivir-resistant strains in the late stage of the infectious cycle. Other novel antiviral drugs under clinical development include AVI-7100, a 20-mer phosphorodiamidate morpholino oligomer (PMO) IV formulation that hinders translation and splicing of mRNA from the matrix gene. EV-077, a dual thromboxane receptor antagonist and thromboxane synthase inhibitor, prevents virus replication by inhibiting prostanoids associated with influenza infections. Aureonitol, a compound obtained from fungi, has shown inhibitory effects against both influenza A and B virus replication by impairing virus adsorption. Monoclonal antibodies, CR6261 and CR8020, bind to the conserved stalk region of HA and inhibit the entry and fusion stages. A broad spectrum human monoclonal antibody (mAb- MEDI8852), which unlike other stem-reactive antibodies, used a rare heavy chain VH (VH6-1) gene, was found to be effective in mice and ferrets and better than oseltamivir [1]. These novel approaches will potentially become effective tools for managing seasonal, zoonotic and pandemic influenza

Influenza viruses have a silent reservoir in the aquatic avian species and continuously pose threat to human population. The avian, swine and other zoonotic influenza infections may range from a mild upper respiratory tract infection to a more severe pneumonia, acute respiratory distress syndrome and even death. Humans can be infected with a wide range of avian [subtypes A(H5N1), A(H7N9), and A(H9N2)] and swine [subtypes A(H1N1), A(H1N2) and A(H3N2)] influenza viruses. Although sustained human to human transmission is lacking, these viruses can be transmitted when there is a direct contact with infected animals or contaminated environments. The virus shows a tremendous potential to mutate, re-assort and give rise novel variants to evade host immunity and vaccination strategies. The emergence of antiviral mutants has further worsened the worldwide control measures. Although management of influenza has been a challenging task owing to its large reservoir and ability to mutate rapidly, the disease can be controlled in the animal source to decrease the risk to human population. With advancements in modern diagnostic methods, vaccination and antiviral strategies, the annual epidemics and

[102, 103], and the use of influenza-virus-like particles as vaccines [104].

virus infections.

46 Influenza - Therapeutics and Challenges

**8. Conclusions**

occasional pandemics can be managed efficiently.

The public health threats from influenza viruses have always been a global concern. They are not only responsible for annual epidemics throughout the world, but also affect quality of life and have negative impacts on the economy due to frequent school and work place absenteeism. The frequencies of influenza infections have further increased due to co-mingling in shared humananimal environment. The virus is known to acquire antigenic shift and drifts and thus pose challenges in control measures and management. Advancements in vaccination strategies, discovery of novel drugs and antiviral therapeutics along with development of a universal influenza vaccine are promising approaches toward the management of future epidemics and pandemics.
