Influenza Treatment: Limitations of Antiviral Therapy and Advantages of Drug Combination Therapy

Abstract

Influenza infection is serious and debilitating for humans and animals. The influenza virus undergoes incessant mutation, segment recombination, and genome reassortment. As a result, new epidemics and pandemics are expected to emerge, making the elimination challenging of the disease. Antiviral therapy has been used for the treatment of influenza since the development of amantadine in the 1960s; however, its use is hampered by the emergence of novel strains and the development of drug resistance. Thus, combinational therapy with two or more antivirals or immunomodulators with different modes of action is the optimal strategy for the effective treatment of influenza infection. In this review, we describe current options for combination therapy, their performance, and constraints imposed by resistance, calling attention to the advantages of combination therapy against severe influenza infections. We also discuss the challenges of influenza therapy and the limitations of approved antiviral drugs.

Antiviral options and therapeutics against influenza: history, latest developments and future prospects

“…The combination therapy also supports reduced drug toxicity. It can either target the same viral protein, two or more viral proteins of influenza or it can also target host and virus associate molecular mechanisms ( Shen et al., 2015 ; Batool et al., 2023 ).…”

Heteromultivalent Ligand Display on Reversible Self-Assembled Monolayers (rSAMs): A Fluidic Platform for Tunable Influenza Virus Recognition

“…NA, a 240 kDa tetrameric glycoprotein, catalyzes the cleavage of terminal sialic acids on the surface of the cells, helping an incoming virus to access the cell and a newly formed virus to escape it. The protein is the target of NA inhibitors (NAIs) that are currently used as emergency antiviral drugs . Due to the high mutation rate of IAVs, several NAI-resistant strains have emerged, some with enhanced infectivity.…”

Evaluation of the Polysaccharide “Immeran” Activity in Syrian hamsters’ Model of SARS-CoV-2

“…The World Health Organization recommends vaccination as the main means of combating the new coronavirus infection [ 5 ]; however, its effectiveness is limited due to the rapid variability of circulating viruses [ 6 ]. In addition, any vaccine is directed against a specific target and, therefore, in addition to vaccination, WHO recommends the use of antiviral drugs, which have their own limitations of applicability [ 7 , 8 , 9 ].…”