Reversal of Infected Host Gene Expression Identifies Repurposed Drug Candidates for COVID-19

Jing Xing; Rama Shankar; Aleksandra Drelich; Shreya Paithankar; Eugene Chekalin; Thomas Dexheimer; Surender Rajasekaran; Chien-Te Kent Tseng; Bin Chen

Organization (WHO) declared this rapidly spreading and highly pathogenic COVID-19 first a global public health emergency and then a pandemic. As SARS-CoV-2 infection continues to endanger lives, effective therapeutics are urgently needed. Repurposing existing drugs could be an efficient and timely means of identifying drugs that have activity against coronavirus. There are a few repurposed drugs such as lopinavir/ritonavir, baricitinib, remdesivir and chloroquine currently under clinical investigation 5, 6 . These drugs are expected to target key steps of viral entry, or specific proteins involved in viral replication, including viral proteases 7 . In addition to viral replication, the viral pathogen associated molecular pattern (PAMP) (e.g., immune dysfunction and endoplasmic reticulum stress, Figure 1A ) could be targeted to improve the clinical outcome 8 . PAMPs-mediated signaling pathways are attractive drug targets to alleviate diseases caused by human pathogens. Therefore, effectively targeting these pathways to stop the progression to ARDS caused by SARS-CoV-2 might save lives. Independent of SARS-CoV-2 infection, in aging adult populations, ARDS is associated with mortality rates of 30-50% 9 . Thus, a methodical and unbiased search for new drug candidates from a large drug library could uncover agents that have potential to arrest the infection and ameliorate its effect. To accomplish this, we sought to target infection-induced genes in the host cells, hoping to mitigate disease progression and alleviate symptoms.