Vicenin-2 for COVID-19

AbstractThe current severe situation of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has not been reversed and posed great threats to global health. Therefore, there is an urgent need to find out effective antiviral drugs. The 3-chymotrypsin-like protease (3CLpro) in SARS-CoV-2 serve as a promising anti-virus target due to its essential role in the regulation of virus reproduction. Here, we report an improved integrated approach to identify effective 3CLpro inhibitors from effective Chinese herbal formulas. With this approach, we identified the 5 natural products (NPs) including narcissoside, kaempferol-3-O-gentiobioside, rutin, vicenin-2 and isoschaftoside as potential anti-SARS-CoV-2 candidates. Subsequent molecular dynamics simulation additionally revealed that these molecules can be tightly bound to 3CLpro and confirmed effectiveness against COVID-19. Moreover, kaempferol-3-o-gentiobioside, vicenin-2 and isoschaftoside were first reported to have SARS-CoV-2 3CLpro inhibitory activity. In summary, this optimized integrated strategy for drug screening can be utilized in the discovery of antiviral drugs to achieve rapid acquisition of drugs with specific effects on antiviral targets.

Respiratory viral infections, including influenza and coronaviruses, present significant health risks worldwide. The recent COVID‐19 pandemic highlights the urgent need for novel and effective antiviral agents. The host cell protease, transmembrane serine protease 2 (TMPRSS2), facilitates viral pathogenesis by playing a critical role in viral invasion and disease progression. This protease is coexpressed with the viral receptors of angiotensin‐converting enzyme 2 (ACE2) for SARS‐CoV‐2 in the human respiratory tract and plays a significant role in activating viral proteins and spreading. TMPRSS2 activates the coronavirus spike (S) protein and permits membrane fusion and viral entry by cleaving the virus surface glycoproteins. It also activates the hemagglutinin (HA) protein, an enzyme necessary for the spread of influenza virus. TMPRSS2 inhibitors can reduce viral propagation and morbidity by blocking viral entry into respiratory cells and reducing viral spread, inflammation, and disease severity. This review examines the role of TMPRSS2 in viral replication and pathogenicity. It also offers potential avenues to develop targeted antivirals to inhibit TMPRSS2 function, suggesting a possible focus on targeted antiviral development. Ultimately, the review seeks to contribute to improving public health outcomes related to these viral infections.

AbstractType-II transmembrane serine proteases are effective pharmacological targets for host defence against viral entry and in certain cancer cell progressions. These serine proteases cleave viral spike proteins to expose the fusion peptide for cell entry, which is essential to the life cycle of the virus. TMPRSS2 inhibitors can also fight against respiratory viruses that employ them for cell entry. Our study combining virtual screening, all-atom molecular dynamics, and well-tempered metadynamics simulation identifies vicenin-2, neohesperidin, naringin, and rhoifolin as promising TMPRSS2 antagonists. The binding energies obtained are − 16.3, − 15.4, − 13.6, and − 13.8 kcal/mol for vicenin-2, neohesperidin, naringin, and rhoifolin respectively. The RMSD, RMSF, PCA, DCCM, and binding free energy profiles also correlate with the stable binding of these ligands at the active site of TMPRSS2. The study reveals that these molecules could be promising lead molecules for combating future outbreaks of coronavirus and other respiratory viruses.