Non-antiviral therapies for viral infections: Harnessing host mechanisms

Despite advancements in the field of directly acting anti-viral (DAA) therapies, viral infections still continue to pose significant global health challenges. The efficacy of DAAs are often hindered by mutations, origin of new strains, development of resistance and lack of broad spectrum effectiveness. Furthermore, patients with advanced-stage diseases may require higher doses and combinations of different DAA therapies, raising concerns about tolerability and safety. To overcome all these constraints, non-antiviral therapies that focuses on host mechanisms (also known as host-focused therapies) are emerging as an innovative approach. Host focused therapy aims to target the host molecules and pathways that are essential for viral infection and disease progression. Along with addressing the above mentioned challenges, these host focused therapies can also modulate excessive inflammatory responses. Recent advancements in understanding host-virus interactions and the pathways involved in the pathogenesis of severe viral infections from viral entry and replication to disease progression, have accelerated the development of host-focused therapies aimed at combating these infections. This review explores the growing rationale and various opportunities for host-focused therapies for severe viral infections including zika virus, dengue, HIV, influenza, and covid-19 to name a few. In addition, current clinical trial information on various classes of host focused therapies are presented, highlighting their therapeutic potential and significance in the field.