The Inhibition of RNA Viruses by Amaryllidaceae Alkaloids: Opportunities for the Development of Broad-Spectrum Anti-Coronavirus Drugs.

The global COVID-19 pandemic has claimed the lives of millions and disrupted nearly every aspect of human society. Currently, vaccines remain the only widely available medical means to address the cause of the pandemic, the SARS-CoV-2 virus. Unfortunately, current scientific consensus deems the emergence of vaccine-resistant SARS-CoV-2 variants highly likely. In this context, the design and development of broad-spectrum, small-molecule based antiviral drugs has been described as a potentially effective, alternative medical strategy to address circulating and re-emerging CoVs. Small molecules are well-suited to target the least-rapidly evolving structures within CoVs such as highly conserved RNA replication enzymes, and this renders them less vulnerable to evolved drug resistance. Examination of the vast literature describing the inhibition of RNA viruses by Amaryllidaceae alkaloids suggests that future, broad-spectrum anti-CoV drugs may be derived from this family of natural products.

Potential of coronavirus 3C-like protease inhibitors for the development of new anti-SARS-CoV-2 drugs: Insights from structures of protease and inhibitors.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), similar to SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV), which belong to the same Betacoronavirus genus, induces severe acute respiratory disease that is a threat to human health. Since the outbreak of infection by SARS-CoV-2 began, which causes coronavirus disease 2019 (COVID-19), the disease has rapidly spread worldwide. Thus, a search for effective drugs able to inhibit SARS-CoV-2 has become a global pursuit. The 3C-like protease (3CLpro), which hydrolyses viral polyproteins to produce functional proteins, is essential for coronavirus replication and is considered an important therapeutic target for diseases caused by coronaviruses, including COVID-19. Many 3CLpro inhibitors have been proposed and some new drug candidates have achieved success in preclinical studies. In this review, we briefly describe recent developments in determining the structure of 3CLpro and its function in coronavirus replication and summarise new insights into 3CLpro inhibitors and their mechanisms of action. The clinical application prospects and limitations of 3CLpro inhibitors for COVID-19 treatment are also discussed.