Insights into molecular mechanisms underlying COVID-19 pathogenesis and potential therapeutics

ABSTRACT

The coronavirus disease 2019 is a disease caused by severe acute respiratory syndrome coronavirus 2 and continues to pose a global threat resulting in thousands of deaths. In the absence of effective therapeutics, implementation of non-pharmaceutical interventions still remains an important prevention strategy, while various vaccine candidates are either approved or in clinical trials, several drugs are also being tested in pre-clinical studies for their potential for repurposing to treat the coronavirus disease 2019. The mechanistic details underlying disease pathogenesis and therapeutic efficacy of various drugs are rapidly emerging, which will be useful for fast-tracking pharmaceutical leads to clinical utility. The current review details the mechanistic understanding of viral pathogenesis including host cell interactions, viral replication, altered host cell processes, cytokine release syndrome and the role of coagulation pathway, renin angiotensin system and kallikrein-bradykinin pathways in acute respiratory distress syndrome. Further, a detailed overview of therapeutic candidates including antibodies, targeted enzyme inhibitors, drugs that showed clinical efficacy and drugs with anti-severe acute respiratory syndrome coronavirus 2 activities in pre-clinical models are discussed. Additionally, the approval and availability of various vaccines and their mechanism of action are also detailed. Importantly, emerging clinical evidence regarding immune biomarkers that help in patient stratification into moderate or severe cases are highlighted that may aid in reducing mortality by choosing appropriate treatment strategies. Taken together, the report gives up to date mechanistic information on disease pathogenesis and potential therapeutics. © 2021 Indian Pharmaceutical Association. All rights reserved.