ABSTRACT
Since COVID-19 emerged in 2019, significant levels of suffering and disruption have been caused on a global scale. Although vaccines have become widely used, the virus has shown its potential for evading immunities or acquiring other novel characteristics. Whether current drug treatments are still effective for people infected with Omicron remains unclear. Due to the long development cycles and high expense requirements of de novo drug development, many researchers have turned to consider drug repositioning in the search to find effective treatments for COVID-19. Here, we review such drug repositioning and combination efforts towards providing better handling. For potential drugs under consideration, aspects of both structure and function require attention, with specific categories of sequence, expression, structure, and interaction, the key parameters for investigation. For different data types, we show the corresponding differing drug repositioning methods that have been exploited. As incorporating drug combinations can increase therapeutic efficacy and reduce toxicity, we also review computational strategies to reveal drug combination potential. Taken together, we found that graph theory and neural network were the most used strategy with high potential towards drug repositioning for COVID-19. Integrating different levels of data may further improve the success rate of drug repositioning.