Vicenin 2 for COVID-19

Abstract Aims The aim of the present review was to highlight natural product investigations in silico and in vitro to find plants and chemicals that inhibit or stimulate angiotensin-converting enzyme 2 (ACE-2). Background The global reduction of incidents and fatalities attributable to infections with SARS-CoV-2 is one of the most public health problems. In the absence of specific therapy for coronavirus disease 2019 (COVID-19), phytocompounds generated from plant extracts may be a promising strategy worth further investigation, motivating researchers to evaluate the safety and anti-SARS-CoV-2 effectiveness of these ingredients. Objective To review phytochemicals in silico for anti-SARS-CoV-2 activity and to assess their safety and effectiveness in vitro and in vivo. Methods The present review was conducted using various scientific databases and studies on anti-SARS-CoV-2 phytochemicals were analyzed and summarized. The results obtained from the in silico screening were subjected to extraction, isolation, and purification. The in vitro studies on anti-SarcoV-2 were also included in this review. In addition, the results of this research were interpreted, analyzed, and documented on the basis of the bibliographic information obtained. Results This review discusses recent research on using natural remedies to cure or prevent COVID-19 infection. The literature analysis shows that the various herbal preparations (extracts) and purified compounds can block the replication or entrance of the virus directly to carry out their anti-SARS-CoV-2 effects. It is interesting to note that certain items can prevent SARS-CoV-2 from infecting human cells by blocking the ACE-2 receptor or the serine protease TMPRRS2. Moreover, natural substances have been demonstrated to block proteins involved in the SARS-CoV-2 life cycle, such as papain- or chymotrypsin-like proteases. Conclusion The natural products may have the potential for use singly or in combination as alternative drugs to treat/prevent COVID-19 infection, including blocking or stimulating ACE-2. In addition, their structures may provide indications for the development of anti-SARS-CoV-2 drugs.

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.

Abstract Objectives The study aims to explore the potential of medicinal plants and their phytoconstituents as effective inhibitors of the coronavirus disease 2019 (COVID-19), caused by the SARS-CoV-2 virus. The focus is on investigating specific medicinal plants known for their pharmacological properties, such as: antioxidant, anti-inflammatory, and immunomodulatory effects, to determine their viability in developing COVID-19 treatments. Materials and methods This study involves a comprehensive study of medicinal plants, including: Withania somnifera (Ashwagandha) and Ocimum sanctum (Holy Basil), known for their beneficial health effects. Molecular docking studies were conducted to assess the interactions between phytoconstituents from these plants and SARS-CoV-2 proteins. The compounds’ drug-like characteristics and safety profiles were also evaluated to determine their potential as therapeutic agents. Results The molecular docking studies revealed that the phytoconstituents from the studied medicinal plants exhibit favourable interactions with SARS-CoV-2 proteins, suggesting their potential as therapeutic targets. These compounds demonstrated promising drug-like characteristics and safety profiles, indicating their suitability for further development as COVID-19-fighting medications. Discussion The results indicate that medicinal plants and their bioactive substances hold significant potential for developing therapies against COVID-19. The ability of these organic substances to interact with key viral proteins and provide various therapeutic benefits highlights their potential as multi-functional treatment options. However, further research is necessary to confirm these findings and to understand the full scope of their therapeutic efficacy and safety in clinical settings. Conclusions Medicinal plants and their phyto-constituents represent a promising avenue for developing effective treatments for COVID-19. The favourable interactions with SARS-CoV-2 proteins and the promising drug-like characteristics observed in this study suggest that these natural compounds could be integral in the fight against the COVID-19 pandemic. Further research and clinical trials are essential to fully validating their potential and translating these findings into practical medical applications.

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.

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.