A KSHV-targeted small molecule efficiently blocks SARS-CoV-2 infection via inhibiting expression of EGFR and Cyclin...

Area of Science:

• Virology and Natural Product Chemistry
• Oncology and Infectious Diseases

Background:

• The COVID-19 pandemic presents challenges with co-infections, particularly SARS-CoV-2 and Kaposi's sarcoma-associated herpesvirus (KSHV).
• Lack of effective bi-targeted drugs for these co-infections increases patient mortality.
• Cambogin shows promise in KSHV-infected tumor regression, but its effect on SARS-CoV-2 is unknown.

Purpose of the Study:

• To investigate the potential of Cambogin as a bi-targeted therapeutic agent against SARS-CoV-2 and KSHV co-infections.
• To elucidate the molecular mechanisms underlying Cambogin's action on host genes targeted by both viruses.

Main Methods:

• Bioinformatics analysis to identify host genes commonly affected by SARS-CoV-2 and KSHV.
• In vitro and in vivo studies to assess Cambogin's efficacy against SARS-CoV-2 replication and KSHV-induced tumors.
• Analysis of the transcriptional factor (TF)-miRNA co-regulatory network.

Main Results:

• Cambogin targets 46 host genes involved in inflammation, phosphorylation, metabolism, and stress response, common to both SARS-CoV-2 and KSHV.
• Cambogin significantly inhibits SARS-CoV-2 replication and virion production in vitro and in vivo by downregulating EGFR and Cyclin A2.
• Cambogin simultaneously suppresses SARS-CoV-2 infection and KSHV-induced tumor growth in a murine xenograft model.

Conclusions:

• Cambogin demonstrates dual efficacy against SARS-CoV-2 and KSHV co-infection.
• Cambogin represents a potential therapeutic strategy for COVID-19 patients, especially those with KSHV co-infection.
• Targeting common host pathways offers a novel approach for treating viral co-infections.