The convergent evolution of influenza A virus: Implications, therapeutic strategies and what we need to know

•Influenza A virus (IAV) has contributed to multiple pandemics for decades.•Antiviral resistance and immune evasion have become more common over time.•Drug repositioning is a valuable and effective means against the IAV.•Various antiviral and vaccination strategies are vital to contain the spread of IAV.•Evolution of IAV holds a critical significance amid the global COVID-19 outbreak. Influenza virus infection, more commonly known as the ‘cold flu’, is an etiological agent that gives rise to recurrent annual flu and many pandemics. Dated back to the 1918- Spanish Flu, the influenza infection has caused the loss of many human lives and significantly impacted the economy and daily lives. Influenza virus can be classified into four different genera: influenza A-D, with the former two, influenza A and B, relevant to humans. The capacity of antigenic drift and shift in Influenza A has given rise to many novel variants, rendering vaccines and antiviral therapies useless. In light of the emergence of a novel betacoronavirus, the SARS-CoV-2, unravelling the underpinning mechanisms that support the recurrent influenza epidemics and pandemics is essential. Given the symptom similarities between influenza and covid infection, it is crucial to reiterate what we know about the influenza infection. This review aims to describe the origin and evolution of influenza infection. Apart from that, the risk factors entail the implication of co-infections, especially regarding the COVID-19 pandemic is further discussed. In addition, antiviral strategies, including the potential of drug repositioning, are discussed in this context. The diagnostic approach is also critically discussed in an effort to understand better and prepare for upcoming variants and potential influenza pandemics in the future. Lastly, this review encapsulates the challenges in curbing the influenza spread and provides insights for future directions in influenza management. [Display omitted]