Rubitecan for COVID-19

Respiratory viral infections, including influenza and coronaviruses, present significant health risks worldwide. The recent COVID‐19 pandemic highlights the urgent need for novel and effective antiviral agents. The host cell protease, transmembrane serine protease 2 (TMPRSS2), facilitates viral pathogenesis by playing a critical role in viral invasion and disease progression. This protease is coexpressed with the viral receptors of angiotensin‐converting enzyme 2 (ACE2) for SARS‐CoV‐2 in the human respiratory tract and plays a significant role in activating viral proteins and spreading. TMPRSS2 activates the coronavirus spike (S) protein and permits membrane fusion and viral entry by cleaving the virus surface glycoproteins. It also activates the hemagglutinin (HA) protein, an enzyme necessary for the spread of influenza virus. TMPRSS2 inhibitors can reduce viral propagation and morbidity by blocking viral entry into respiratory cells and reducing viral spread, inflammation, and disease severity. This review examines the role of TMPRSS2 in viral replication and pathogenicity. It also offers potential avenues to develop targeted antivirals to inhibit TMPRSS2 function, suggesting a possible focus on targeted antiviral development. Ultimately, the review seeks to contribute to improving public health outcomes related to these viral infections.

AbstractTo attain promising pharmacotherapies, researchers have applied drug repurposing (DR) techniques to discover the candidate medicines to combat the coronavirus disease 2019 (COVID-19) outbreak. Although many DR approaches have been introduced for treating different diseases, only structure-based DR (SBDR) methods can be employed as the first therapeutic option against the COVID-19 pandemic because they rely on the rudimentary information about the diseases such as the sequence of the severe acute respiratory syndrome coronavirus 2 genome. Hence, to try out new treatments for the disease, the first attempts have been made based on the SBDR methods which seem to be among the proper choices for discovering the potential medications against the emerging and re-emerging infectious diseases. Given the importance of SBDR approaches, in the present review, well-known SBDR methods are summarized, and their merits are investigated. Then, the databases and software applications, utilized for repurposing the drugs against COVID-19, are introduced. Besides, the identified drugs are categorized based on their targets. Finally, a comparison is made between the SBDR approaches and other DR methods, and some possible future directions are proposed.