Natural agents targeting Hsp90 co-chaperones could be promising candidates for viral resistance prevention

Viral infections have constituted a serious menace to global health. The emergence of resistant strains resulting from adaptive evolution poses a great challenge to virus control. Heat shock protein 90 (Hsp90) can shepherd virus-mutated proteins to fold into functional conformations. Therefore, inhibiting Hsp90 can block the evolution of viruses. However, none of the current Hsp90 inhibitors has been approved because of the unacceptable side effects. Considering the importance of co-chaperones for Hsp90 conformational cycle, inhibiting Hsp90 through co-chaperones may be a safe and effective strategy. Some natural agents can bind the co-chaperones to indirectly modulate Hsp90 activity with low toxicity. Besides, some of these natural agents indicate antiviral effects. Therefore, natural products are highly expected to be used as virus resistance preventives through targeting the co-chaperones of Hsp90.