Recent advances in 3CL<sup>pro</sup> inhibitors from Chinese herbs
aZhongguo kexue（2022）
Severe acute respiratory syndromes caused by highly pathogenic β-coronaviruses (such as SARS-CoV-2, SARS-CoV and MERS-CoV) still lack safe and effective pharmacotherapy. Although Chinese herbal medicines have shown unique benefits for treating these diseases, their active substances and mechanisms have not been fully revealed. Coronavirus 3C-like proteases (3CLpro), a class of cysteine hydrolases that are highly conserved in β-coronaviruses and play a critical role in viral replication, have been recognized as a crucial target for preventing and treating a range of coronavirus diseases including COVID-19. Recent studies have shown that a variety of Chinese herbal extracts and their constituents such as flavonoids, triterpenoids, and phenolic compounds can inhibit 3CLpro, providing novel lead compounds for developing antiviral drugs. In this review, we systematically summarize the 3CLpro inhibitory activities and inhibitory mechanisms of herbal constituents against SARS-CoV-2 3CLpro, MERS-CoV 3CLpro and SARS-CoV 3CLpro. Meanwhile, we highlight the challenges in this field, and provide an outlook for the future direction for developing natural-derived 3CLpro inhibitors and novel anti-coronavirus drugs. Collectively, all information and knowledge presented here will be helpful for clarifying the active substances and mechanisms of anti-coronavirus herbal medicines, as well as providing new insights or inspiration for developing 3CLpro inhibitors and broad-spectrum anti-coronavirus drugs derived from Chinese herbal medicines.
